Atrial natriuretic peptide (ANP) is a peptide hormone that has potent natriuretic, diuretic, vasodilator, sympatholytic, and renin - and aldos-terone - suppressing activities and is involved in the regulation of volum...Atrial natriuretic peptide (ANP) is a peptide hormone that has potent natriuretic, diuretic, vasodilator, sympatholytic, and renin - and aldos-terone - suppressing activities and is involved in the regulation of volume and electrolyte balance and blood pressure. Further, ANP has also been shown to inhibit cellular growth, proliferation and induce apoptosis in a variety of cell lines, including vascular smooth muscle cells and cardiac myocytes. Recent studies have demonstrated that ANP is not only involved in blood pressure and volume homeostasis but also in the direct regulation of cardiac growth. We and other investigators have demonstrated the existence of natriuretic peptide receptors in the heart and cardiac cells, suggesting that ANP has direct actions on cardiac tissue. Several recent in vivo studies have suggested that statement of ANP is inversely related to cardiac growth/hypertrophy. Transgenic mice overexpressing ANP have lower heart weight and blood pressure than wild type mice. Conversely, we demonstrated that transgenic mice with homozygous disruption of the pro - ANP gene (Nppa) (ANP -/- mice) have no circulating or tissue ANP and exhibit significant cardiac hypertrophy and increased blood pressure. Further, transgenic mice lacking a functional natriuretic peptide receptor A (NPR-A) gene display elevated blood pressure and marked cardiac hypertrophy. The role of ANP in the development of cardiac hypertrophy in response to hemodynamic stress has not previously been studied. Our previous studies demonstrated that ANP - / -mice with hypoxia - induced pulmonary hypertension and high salt diet - induced systemic hypertension develop greater cardiac enlargement than their wild type controls under same experimental conditions, suggest-ing that cardiac enlargement in ANP -/- mice might, at least in part, be related to increased afterload. In a recent study, we used ANP -/- mice to further test the hypothesis that ANP plays an important role in protecting against the development of cardiac enlargement induced by volume overload stress. Adult (8-10 wk old) male ANP -/- and wild type ANP+/+ mice underwent an aorto - caval fistula (ACF) or sham surgery and were subjected to echocardiographic examination at 2 wks. Mean arterial pressure (MAP) and atrial, left ventricular (LV) and right ventricular (RV) mass were greater in sham - operated ANP-/-mice than in ANP+/+mice. MAP decreased following ACF to a similar extent in both genotypes. ACF induced significant concentric cardiac enlargement in both genotypes. Cardiac enlargement and lung weight increased to a greater extent in ANP - / - mice than in ANP+/ + mice, indicating that disrupted ANP statement worsens ACF- induced cardiac enlargement and pulmonary congestion. LV function (velocity of circumferential shortening [VCFr], circumferential stress, fraction shortening, fraction shortening, and e-jection time and fraction) assessed by echocardiography did not differ between sham - operated ANP + / + and ANP - / - mice and remained unchanged after ACF. These findings indicate that ANP deletion results in biventricular enlargement and an exaggerated response to the stress of volume overload. This support the hypothesis that ANP has direct antihypertrophic and car-dioprotective actions in heart. Further study is needed to dissect the contributions of increased afterload from those of removing the antihypertrophic effects of ANP to basal and stress induced cardiac enlargement in this animal model.展开更多
AIM:To investigate atrial natriuretic peptide(ANP) secretion from gastric mucosa and the relationship between the ANP/natriuretic peptide receptor type A (NPR-A)pathway and diabetic gastroparesis. METHODS:Male imprint...AIM:To investigate atrial natriuretic peptide(ANP) secretion from gastric mucosa and the relationship between the ANP/natriuretic peptide receptor type A (NPR-A)pathway and diabetic gastroparesis. METHODS:Male imprinting control region(ICR)mice (4 wk old)were divided into two groups:control mice, and streptozotocin-induced diabetic mice.Eight weeks after injection,spontaneous gastric contraction was recorded by using physiography in control and streptozotocin-induced diabetic mice.The ANP-positive cells in gastric mucosa and among dispersed gastric epithelial cells were detected by using immunohistochemistry and flow cytometry,respectively.ANP and natriureticpeptide receptor type A(NPR-A)gene expression in gastric tissue was observed by using the reverse transcriptase polymerase chain reaction. RESULTS:The frequency of spontaneous gastric contraction was reduced from 12.9±0.8 cycles/min in the control group to 8.4±0.6 cycles/min in the diabetic mice(n=8,P<0.05).However,the amplitude of contraction was not significantly affected in the diabetic group.The depletion of interstitial cells of Cajal in the gastric muscle layer was observed in the diabetic mice.ANP-positive cells were distributed in the gastric mucosal layer and the density index of ANP-positive cells was increased from 20.9±2.2 cells/field in control mice to 51.8±2.9 cells/field in diabetic mice(n=8, P<0.05).The percentage of ANP-positive cells among the dispersed gastric epithelial cells was increased from 10.0%±0.9%in the control mice to 41.2%± 1.0%in the diabetic mice(n=3,P<0.05).ANP and NPR-A genes were both expressed in mouse stomach, and the expression was significantly increased in the diabetic mice. CONCLUSION:These results suggest that the ANP/ NPR-A signaling pathway is upregulated in streptozotocin-induced diabetic mice,and contributes to the development of diabetic gastroparesis.展开更多
Objective:To understand the role of ANP mRNA transcription regulation in gpl30-mediated cardiomyocyte hypertrophy,and the involved mitogen-aetivated protein kinase kinase(MEK)-extracellular signal-regulated kinase(ERK...Objective:To understand the role of ANP mRNA transcription regulation in gpl30-mediated cardiomyocyte hypertrophy,and the involved mitogen-aetivated protein kinase kinase(MEK)-extracellular signal-regulated kinase(ERK,also called p42/p44 MAPK)signaling pathway.Methods:isolated neonatal ventricular myocytes were treated with different concentrations of CT-1(10^(-9),10^(-8)and 10^(-7)mol/L).MTT was used to analyze the viability and RT-PCR was used to detect ANP mRNA levels in eardiomyocyte.To inhibit p42/p44 MAPK activity in hypertrophic cardiomyoeytes,the cells were pretreated with a specific MEKI inhibitor.Results:CT-1significantly induced ANP mRNA expression and the viability of canliomyocytes in a doseand time-dependent manner.Furthermore,blocking p42/p44 MAPK activity by the special MEk1 inhibitor uprcgulatcd the ANP mKNA.Conclusions:p42/p44 MAPK have an important role in suppressing ANP mRNA transcription and cell activity in gpl30-mediated hypertrophic ventricular myocytes.展开更多
AIM: To evaluate the value of plasma N-terminal pro- brain natriuretic peptide (NT-proBNP) level for predicting postoperative atrial fibrillation (AF) in patients undergoing surgery for esophageal carcinoma. METHODS: ...AIM: To evaluate the value of plasma N-terminal pro- brain natriuretic peptide (NT-proBNP) level for predicting postoperative atrial fibrillation (AF) in patients undergoing surgery for esophageal carcinoma. METHODS: NT-proBNP levels were measured in 142 patients 24 h before and 1 h after surgery for esophageal carcinoma. All patients having a preoperative cardiac diagnosis by electrocardiogram (ECG), remained under continuous monitoring for at least 48 h after surgery, and then underwent clinical cardiac evaluation until discharge. RESULTS: Postoperative AF occurred in 11 patients (7.7%). AF patients were significantly older (69.6 ± 12.2 years vs 63.4 ± 13.3 years, P = 0.031) than non-AF patients. There were no significant differences in history of diabetes mellitus, sex distribution, surgical approach, anastomosis site, intraoperative hypotension and postoperative fever. The preoperative plasma NT-proBNP level was significantly higher in patients who developed postoperative AF (121.3 ± 18.3 pg/mL vs 396.1 ± 42.6 pg/mL, P = 0.016). After adjustment for age, gender, chronic obstructive pulmonary disease (COPD), history of cardiac diseases, hypertension, postoperative hypoxia and thoracic-gastric dilation, NT-proBNP levels were found to be associated with the highest risk factor for postoperative AF (odds ratio = 4.711, 95% CI = 1.212 to 7.644, P = 0.008).CONCLUSION: An elevated perioperative plasma BNP level is a strong and independent predictor of postoperative AF in patients undergoing surgery for esophageal carcinoma. This finding has important implications for identifying patients at higher risk of postoperative AF who should be considered for preventive antiarrhythmic therapy.展开更多
BACKGROUND The prevalence of cardiovascular diseases,especially heart failure,continues to rise worldwide.In heart failure,increasing levels of circulating atrial natriuretic peptide(ANP)and brain natriuretic peptide(...BACKGROUND The prevalence of cardiovascular diseases,especially heart failure,continues to rise worldwide.In heart failure,increasing levels of circulating atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP)are associated with a worsening of heart failure and a poor prognosis.AIM To test whether a high concentration of BNP would inhibit relaxation to ANP.METHODS Pulmonary arteries were dissected from disease-free areas of lung resection,as well as pulmonary artery rings of internal diameter 2.5–3.5 mm and 2 mm long,were prepared.Pulmonary artery rings were mounted in a multiwire myograph,and a basal tension of 1.61gf was applied.After equilibration for 60 min,rings were pre-constricted with 11.21μmol/L PGF2α(EC80),and concentration response curves were constructed to vasodilators by cumulative addition to the myograph chambers.RESULTS Although both ANP and BNP were found to vasodilate the pulmonary vessels,ANP is more potent than BNP.pEC50 of ANP and BNP were 8.96±0.21 and 7.54±0.18,respectively,and the maximum efficacy(Emax)for ANP and BNP was-2.03 gf and-0.24 gf,respectively.After addition of BNP,the Emax of ANP reduced from-0.96gf to-0.675gf(P=0.28).CONCLUSION BNP could be acting as a partial agonist in small human pulmonary arteries,and inhibits relaxation to ANP.Elevated levels of circulating BNP could be responsible for the worsening of decompensated heart failure.This finding could also explain the disappointing results seen in clinical trials of ANP and BNP analogues for the treatment of heart failure.展开更多
AIM: To evaluate the effect of ANP on warm I/R injury in a porcine THVE model. METHODS: Miniature pigs (mini-pigs) weighing 16-24 kg were observed for 120 min after reperfusion following 120 min of THVE. The animals w...AIM: To evaluate the effect of ANP on warm I/R injury in a porcine THVE model. METHODS: Miniature pigs (mini-pigs) weighing 16-24 kg were observed for 120 min after reperfusion following 120 min of THVE. The animals were divided into two groups. ANP (0.1 μg/kg per min) was administered to the ANP group (n = 7), and vehicle was administered to the control group (n = 7). Either vehicle or ANP was intravenously administered from 30 min before the THVE to the end of the experiment. Arterial blood was collected to measure AST, LDH, and TNF-α. Hepatic tissue blood ? ow (HTBF) was also measured. Liver specimens were harvested for p38 MAPK analysis and histological study. Those results were compared between the two groups. RESULTS: The AST and LDH levels were lower in the ANP group than in the control group; the AST levels were signifi cantly different between the two groups (60 min: 568.7 ± 113.3 vs 321.6 ± 60.1, P = 0.038 < 0.05, 120 min: 673.6 ± 148.2 vs 281.1 ± 44.8, P = 0.004 < 0.01). No signifi cant difference was observed in the TNF-α levels between the two groups. HTBF was higher in the ANP group, but the difference was not signif icant. A signifi cantly higher level of phosphorylated p38 MAPK was observed in the ANP group compared to the controlgroup (0 min: 2.92 ± 1.1 vs 6.38 ± 1.1, P = 0.011 < 0.05).Histological tissue damage was milder in the ANP group than in the control group. CONCLUSION: Our results show that ANP has a protective role in I/R injury with p38 MAPK activation in a porcine THVE model.展开更多
The present study investigated a possible mechanism for endogenous endothelin-1 (ET-1) regulation of atrial natriuretic peptide (ANP) secretion in isolated perfused acute hypoxic rabbit atria. Acute hypoxia significan...The present study investigated a possible mechanism for endogenous endothelin-1 (ET-1) regulation of atrial natriuretic peptide (ANP) secretion in isolated perfused acute hypoxic rabbit atria. Acute hypoxia significantly enhanced the release of ET-1 and the expression of the ET receptor (ETR) type A and B (ETR<sub>A</sub> and ETR<sub>B</sub>) in atrial tissues, with a concomitant increase in ANP secretion. The ETR<sub>A</sub> or ETR<sub>B</sub> antagonist, BQ123 (0.3 μmol/L) or BQ788 (0.3 μmol/L), respectively attenuated hypoxia-induced ANP secretion. Both antagonists significantly attenuated the levels of hypoxiainduced atrial phosphorylated (p)-extracellular signal-regulated kinase (ERK) and p-protein kinase B (Akt). The ERK and Akt inhibitors, PD098059 (30 μmol/L) and LY294002 (30 μmol/L), respectively mimicked the effect of the ETR antagonists. These results demonstrated that acute hypoxia- mediated atrial ET-1 regulated ANP secretion through ETR and the subsequent mitogenactivated protein kinase (MAPK)/ERK and ETR-phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathways. These pathways may mediate atrial endocrine functions under hypoxic conditions.展开更多
Objective:To explore the protective effect of acupuncture against myocardial injury in rats with stress-induced prehypertension (SIPH) by observing the genetic expression of myocardial endothelin-1 (ET-1) and atrial n...Objective:To explore the protective effect of acupuncture against myocardial injury in rats with stress-induced prehypertension (SIPH) by observing the genetic expression of myocardial endothelin-1 (ET-1) and atrial natriuretic peptide (ANP).Methods:Thirty-six Wistar rats were randomized into three groups:the control group,model group,and model + acupuncture (AP) group (n =12 rats per group).During the 11-day modeling period,the model group and the model + AP group experienced plantar electric stimulation in combination with noise exposure,and daily acupuncture intervention was applied simultaneously in the model + AP group;the control group did not experience modeling or acupuncture.Systolic pressure (SP) was measured the day before modeling began,and on the 3rd,5th,7th,9th,and 11th day after modeling initiation.On the 12th day,histopathological observation of the left ventricle was made with hematoxylin-eosin staining and quantitative genetic expression of myocardial ET-1,and ANP was tested by quantitative real-time polymerase chain reaction (PCR).Results:SP was higher in the model group than the control group on the 3rd,5th,7th,9th,and 11th days (all P <.01).SP in the model + AP group was lower than that in the control group on the 5th and 7th days (respectively,P =.008,P =.002) and on the 9th and 11th days (P =.029,P =.039).Hematoxylin-eosin staining showed normal myocardial cellular structure in the control group.The model group showed disordered arrangement of cardiac cells with morphological changes in some nuclei,including enlargement or dissolution;there was also infiltration of inflammatory cells and proliferation of collagen fibers.In the model + AP group,most of the myocardial cells were normally structured,and only part of the cells had morphological changes with enlarged nuclei or dissolution.Real-time PCR showed that expression of ET-1 and ANP mRNA in the model group was greater than the control group (respectively,P =.024,P =.000101).The model + AP group had lower expression of ET-1 and ANP mRNA compared with the model group (respectively,P =.033,P =.043).Conclusion:Acupuncture may lower blood pressure and downregulate the genetic expression of myocardial ET-1 and ANP in SIPH rats,suggesting a protective effect of acupuncture against myocardial damage.展开更多
Changes in plasma atrial natriuretic peptide(ANP)and serum lipids were observed us-ing dietetic atherosclerosis(AS)models.The results showed that plasma ANP level of the ASgroup was significantly higher than that of t...Changes in plasma atrial natriuretic peptide(ANP)and serum lipids were observed us-ing dietetic atherosclerosis(AS)models.The results showed that plasma ANP level of the ASgroup was significantly higher than that of the control group(14.33±3.58μg/L vs 9.43±3.14μg/L).There was also a marked increase in serum Tch,TG,LDL-ch and VLDL-ch comparedwith the control group(P【0.01),suggesting that release of ANP increased with disturbance ofthe serum lipids and during AS formation,and that change in ANP was closely related to Tchand LDL-ch(P【0.05).Possible mechanisms causing these changes are also discussed.展开更多
The effects of highly-potent atrial natriuretic peptide (HPANP) on circulating re nin-angiotensin-aldos-terone system (RAAS) and cardiac function were studied in an acute ischemic heart failure model. HPANP (6 μg/kg ...The effects of highly-potent atrial natriuretic peptide (HPANP) on circulating re nin-angiotensin-aldos-terone system (RAAS) and cardiac function were studied in an acute ischemic heart failure model. HPANP (6 μg/kg and 3 μg/kg) was infused intracoronarily. It was found that both doses of HPANP could cause significant decrease in plasma renin activity (PRA), angiotensin II (AII) and aldosterone (Ald). After the administraticn of HPANP, PRA, AII and Ald in the coronary sinus were decreased by 73. 2% (P<0.01), 68. o% (P<0.01) and 73. 6% (P<0.01), and the hormones in peripheral venous blood by 63. 3% (P<0.01), 53. 3% (P<0.01) and 64. 9% (P<0.01), respectively at the dose of 6 μg/kg. While PRA, AII and Ald in the coronary sinus and in peripheral venous blood decreased by 55. 9%, 55. 3%, 61. 9%, and 54. 0%, 42. 3%, 53, 3%, respectively at the 3μg/kg dose level. At the higher dose, HPANP increased left ventricular systolic pressure (LVSP, +13. 1%, P<0. 05), +dP/dtmax(+24.1 %, P<0.01), -dp/dtmax (+35.9%, P<0.01), and VCE(+28.9%, P<0.05). Mean arterial pressure and left ventricular end-diastolic pressure (LVEDP) were decreased (-15.0%, P<0.01, and 29. 6%, P<0.01, respectively). In contrast, the lower dose caused no significant changes of LVSP, +dp/dtmex,dp/dtmax and VCE(not including LVEDP, - 20. 5 %, P<0.05). Neither of the doses caused significant changes in heart rate and T value- Normal saline infusion has no effects on cardiac function and circulating RAAS- We conclude that in ischemic heart failure, intracoronary administration of HPANP can significantly suppress the activity of circulating RAAS, and improve cardiac function by reducing pre- and after-load of the heart, but has no direct myocardial effects.展开更多
Background: Sex dimorphism in the prevalence, onset, development and progression of cardiovascular disease (CVD) is well recognized, but the mechanisms whereby sex hormones are believed to confer cardioprotection are ...Background: Sex dimorphism in the prevalence, onset, development and progression of cardiovascular disease (CVD) is well recognized, but the mechanisms whereby sex hormones are believed to confer cardioprotection are still not fully understood. Objective: This study more closely delineates the effect of 17β-Estradiol (E2) on the expression and signaling of the cardiac NP and NOS systems, well-known cardioprotective modulators of the cardiac hypertrophy (CH) response, that both contribute to downstream production of cyclic guanosine 3’,5’-monophosphate (cGMP). Materials and Methods: Ovariectomized (OVX) female ANP+/+ and ANP-/- mice, 6 - 7 weeks old, were subjected to a five-week treatment with E2 (100 μg/100 μL/day) or vehicle (VEH). Left ventricle from these treatment groups, along with that from age-matched male ANP+/+ and ANP-/- mice was used to assess expression of these systems by real-time quantitative PCR (qPCR). Left ventricle tissue and plasma cGMP were measured by enzyme immunoassay to assess alterations in resultant downstream signaling. Results: NP system expression was unchanged across genotype, sex and E2 treatment. Sex-specific differences in NOS system expression were observed;female mice showed an increased expression of NOS system genes that were significantly elevated in all but one of the E2 treatment groups. Left ventricle tissue cGMP remained unchanged across genotype, sex and E2 treatment. Plasma cGMP levels were unchanged in ANP+/+ treatment groups. In ANP-/- treatment groups, plasma cGMP in the female OVX-E2 mice was significantly higher compared to male and female OVX-VEH mice. Conclusion: These findings demonstrate that in the absence of ANP, E2 upregulates cardiac NOS system expression to produce cGMP. This study confirms the importance of the cardiac NOS system in females;this particular system may be a promising future target for sex-specific treatments and therapies for CVD in women.展开更多
Objectives To investigate the possible role of amino-terminal pro-brain natriuretic peptide (NT-proBNP) in the occurrence of atrial fibrillation (AF) after coronary artery bypass grafting (CABG). Methods This st...Objectives To investigate the possible role of amino-terminal pro-brain natriuretic peptide (NT-proBNP) in the occurrence of atrial fibrillation (AF) after coronary artery bypass grafting (CABG). Methods This study group included 70 consecutive patients scheduled for elective off-pump CABG. The patients with ejection fraction (EF) less than 0. 30, history of AF, use of class Ⅰ or Ⅲ antiarrhythmic drug, implanted pacemaker, postoperative myocardial infarction or chest reopening for pericardial tamponade were excluded. Preoperative and postoperative serum NT-proBNP levels were measured by radioimmunoassay technique. Results Postoperative AF occurred in 15 patients (21.4%); these patients had significantly higher median NT-proBNP levels when compared with those without AF after the operation ( P 〈 0. 01 ). Using multivariate logistic regression analyses, an increase in NT-proBNP level after CABG was found to be independently associated with AF ( OR = 3.78, 95% IC = 1.81 - 4. 89, P 〈 0. 01 ). Increased age, diabetes mellitus, preoperative use of β-blocker, proximal right coronary artery involvement, and longer operation time were al- so associated with AF. Conclusions These results indicated that AF was associated with higher NT-proBNP concentrations after off pump CABG; the increase in NT-proBNP after CABG may play an important role in the occurrence of AF after the operation. The further studies are needed to define the reason that lead to higher NT-proBNP concentrations among the patients who present AF after off pump CABG.展开更多
BACKGROUND Natriuretic peptides are involved in the cascade of pathophysiological events occurring in liver cirrhosis,counterbalancing vasoconstriction and anti-natriuretic factors.The effects of natriuretic peptides ...BACKGROUND Natriuretic peptides are involved in the cascade of pathophysiological events occurring in liver cirrhosis,counterbalancing vasoconstriction and anti-natriuretic factors.The effects of natriuretic peptides as treatment of cirrhotic ascites have been investigated only in small studies,and definitive results are lacking.AIM To examine the effects and safety of natriuretic peptides in cirrhosis patients with ascites.METHODS We searched MEDLINE,Web of Science,Scopus,Cochrane Library and Embase for all available studies applying intravenous administration of any natriuretic peptide to patients suffering from cirrhotic ascites.Inclusion was not limited by treatment duration or dose,or by follow-up duration.Both randomised controlled trials and non-randomised studies were eligible for inclusion.The primary outcome was change in renal sodium excretion.Secondary outcomes included safety measures and changes in renal water excretion,plasma aldosterone concentration,and plasma renin activity.RESULTS Twenty-two studies were included.Atrial natriuretic peptide(ANP)was the only intensively studied treatment.Sodium excretion increased in response to continuous ANP infusion and was more pronounced when infusion rates of>30 ng/kg/min were administered compared with≤30 ng/kg/min(P<0.01).Moreover,natriuresis was significantly higher in study subgroups with mild/moderate ascites compared with moderate/severe and refractory ascites(P<0.01).ANP infusions increased renal water excretion,although without reaching a statistically significant dose-response gradient.Plasma aldosterone concentration and plasma renin activity were significantly lower at baseline in study subgroups achieving a negative sodium balance in response to an ANP administration compared with treatment non-responders(P<0.01).Blood pressure decreases occurred less frequently when ANP doses≤30 ng/kg/min were applied.The quality of evidence for a natriuretic response to ANP was low,mainly due to small sample sizes and considerable between-study heterogeneity.Data were sparse for the other natriuretic peptides;B-type natriuretic peptide and urodilatin.CONCLUSION Intravenous ANP infusions increase sodium excretion in patients with cirrhotic ascites.Continuous infusion rates>30 ng/kg/min are the most effective.However,safety increases with infusion rates≤30 ng/kg/min.展开更多
Aims: To characterize the plasma levels of the atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with atrioventricular nodal reentry tachycardia (AVNRT), we measured the plasma levels of...Aims: To characterize the plasma levels of the atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with atrioventricular nodal reentry tachycardia (AVNRT), we measured the plasma levels of these peptides before and during tachycardia. Methods: We included 10 consecutive patients scheduled for ablation of typical AVNRT without structural heart disease. Catheters were inserted in the femoral artery, femoral vein, and coronary sinus (CS) prior to the ablation procedure. Blood samples were drawn before and after 3 min of tachycardia to measure plasma levels of ANP and BNP. Right atrial pressure (RAP) was measured at baseline. Results: Of the 10 patients, in three patients it was not possible to induce tachycardia leaving a total of 7 patients available for analysis. Mean age of the seven included patients was 40 ± 12 years (mean ± SD), five were female. ANP levels increased significantly during tachycardia in the artery (p = 0.0009) and vein (p = 0.003), but only borderline in CS (p = 0.09). BNP levels did not change during tachycardia in any location. Conclusion: ANP levels measured in the peripheral circulation increased acutely during tachycardia due to AVNRT. BNP levels did not increase.展开更多
Compared to their linear counterparts,cyclic peptides show better biological activities,such as antibacterial,immunosuppressive,and anti-tumor activities,and pharmaceutical properties due to their conformational rigid...Compared to their linear counterparts,cyclic peptides show better biological activities,such as antibacterial,immunosuppressive,and anti-tumor activities,and pharmaceutical properties due to their conformational rigidity.However,cyclic peptides could form numerous putative metabolites from potential hydrolytic cleavages and their fragments are very difficult to interpret.These characteristics pose a great challenge when analyzing metabolites of cyclic peptides by mass spectrometry.This study was to assess and apply a software-aided analytical workflow for the detection and structural characterization of cyclic peptide metabolites.Insulin and atrial natriuretic peptide(ANP)as model cyclic peptides were incubated with trypsin/chymotrypsin and/or rat liver S9,followed by data acquisition using TripleTOF?5600.Resultant full-scan MS and MS/MS datasets were automatically processed through a combination of targeted and untargeted peak finding strategies.MS/MS spectra of predicted metabolites were interrogated against putative metabolite sequences,in light of a,b,y and internal fragment series.The resulting fragment assignments led to the confirmation and ranking of the metabolite sequences and identification of metabolic modification.As a result,29 metabolites with linear or cyclic structures were detected in the insulin incubation with the hydrolytic enzymes.Sequences of twenty insulin metabolites were further determined,which were consistent with the hydrolytic sites of these enzymes.In the same manner,multiple metabolites of insulin and ANP formed in rat liver S9 incubation were detected and structurally characterized,some of which have not been previously reported.The results demonstrated the utility of software-aided data processing tool in detection and identification of cyclic peptide metabolites.展开更多
Background An inflammatory response leading to organ dysfunction and failure continues to be a major problem after injury in many clinical conditions such as sepsis, severe burns, and trauma. It is increasingly recogn...Background An inflammatory response leading to organ dysfunction and failure continues to be a major problem after injury in many clinical conditions such as sepsis, severe burns, and trauma. It is increasingly recognized that atrial natriuretic peptide (ANP) possesses a broad range of biological activities, including effects on endothelial function and inflammation. A recent study has revealed that ANP exerts anti-inflammatory effects. In this study we tested the effects of human ANP (hANP) on lung injury in a model of oleic acid (OA)-induced acute lung injury (ALl) in rats. Methods Rats were randomly assigned to three groups (n=6 in each group). Rats in the control group received a 0.9% solution of NaCI (1 ml-kg-l.h1) by continuous intravenous infusion, after 30 minutes a 0.9% solution of NaCI (1 ml/kg) was injected intravenously, and then the 0.9% NaCI infusion was restarted. Rats in the ALl group received a 0.9% NaCI solution (1 ml-kgl-h-~) intravenous infusion, after 30 minutes OA was injected intravenously (0.1 ml/kg), and then the 0.9% NaCI infusion was restarted. Rats in the hANP-treated ALl group received a hANP (0.1 IJg.kg-Lmin~) infusion, after 30 minutes OA was injected intravenously (0.1 ml/kg), and then the hANP infusion was restarted. The anti-inflammation effects of hANP were evaluated by histological examination and determination of serum cytokine levels. Results Serum interleukin (IL)-113, IL-6, IL-10 and tumor necrosis factor (TNF) a were increased in the ALl group at six hours. The levels of all factors were significantly lower in the hANP treated rats (P 〈0.005). Similarly, levels of IL-113, IL-6, IL-10 and TNF-a were higher in the lung tissue in the ALl group at six hours, hANP treatment significantly reduced the levels of these factors in the lungs (P 〈0.005). Histological examination revealed marked reduction in interstitial congestion, edema, and inflammation. Conclusion hANP can attenuate inflammation in OA-induced lung injury in rat model.展开更多
Background Radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) has developed rapidly,and is a commonly performed ablation in many major hospitals throughout the world,due to its satisfactory resul...Background Radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) has developed rapidly,and is a commonly performed ablation in many major hospitals throughout the world,due to its satisfactory results.The aim of this study was to detect the effect of RFCA on C-reactive protein (CRP),brain natriuretic peptide (BNP),and echocardiograph in patients with persistent and permanent AF.Methods A total of 120 patients (71 males,mean age (50.8&#177;12.0) years) with persistent and permanent AF undergoing RFCA under guidance of the Carto merge technique were studied.Left atrial diameter (LAD),right atrial diameter (RAD),left ventricular ejection fraction (LVEF),CRP,and BNP were observed 3,6 and 12 months after RFCA and compared with results before RFCA.The recurrence of atrial arrhythmias was observed 3 and 12 months after the procedure.Results Compared with that before RFCA,LAD and RAD decreased and LVEF increased significantly after RFCA.Meanwhile,the levels of CRP and BNP were reduced significantly at 3,6,and 12 months after RFCA (P〈0.05).In the non-recurrent patients,LVEF was increased significantly compared with the recurrent patients at 3,6,and 12 months after RFCA (P〈0.05).CRP and BNP levels were decreased significantly in the non-recurrent patients compared with the recurrent patients at 3,6,and 12 months after RFCA (P〈0.05).After one or two applications of RFCA,during a follow-up of 12 months,12 patients (10.0%) had AF,10 patients (8.3%) had atrial flutter,and 5 patients had atrial tachycardia (4.2%).Conclusions Conversion of AF to sinus rhythm by RFCA,has been shown to reduce LA size and improve LVEF.It can also significantly decrease the levels of CRP and BNP in patients with persistent and permanent AF and reduce the risk of inflammation and developing heart failure.展开更多
文摘Atrial natriuretic peptide (ANP) is a peptide hormone that has potent natriuretic, diuretic, vasodilator, sympatholytic, and renin - and aldos-terone - suppressing activities and is involved in the regulation of volume and electrolyte balance and blood pressure. Further, ANP has also been shown to inhibit cellular growth, proliferation and induce apoptosis in a variety of cell lines, including vascular smooth muscle cells and cardiac myocytes. Recent studies have demonstrated that ANP is not only involved in blood pressure and volume homeostasis but also in the direct regulation of cardiac growth. We and other investigators have demonstrated the existence of natriuretic peptide receptors in the heart and cardiac cells, suggesting that ANP has direct actions on cardiac tissue. Several recent in vivo studies have suggested that statement of ANP is inversely related to cardiac growth/hypertrophy. Transgenic mice overexpressing ANP have lower heart weight and blood pressure than wild type mice. Conversely, we demonstrated that transgenic mice with homozygous disruption of the pro - ANP gene (Nppa) (ANP -/- mice) have no circulating or tissue ANP and exhibit significant cardiac hypertrophy and increased blood pressure. Further, transgenic mice lacking a functional natriuretic peptide receptor A (NPR-A) gene display elevated blood pressure and marked cardiac hypertrophy. The role of ANP in the development of cardiac hypertrophy in response to hemodynamic stress has not previously been studied. Our previous studies demonstrated that ANP - / -mice with hypoxia - induced pulmonary hypertension and high salt diet - induced systemic hypertension develop greater cardiac enlargement than their wild type controls under same experimental conditions, suggest-ing that cardiac enlargement in ANP -/- mice might, at least in part, be related to increased afterload. In a recent study, we used ANP -/- mice to further test the hypothesis that ANP plays an important role in protecting against the development of cardiac enlargement induced by volume overload stress. Adult (8-10 wk old) male ANP -/- and wild type ANP+/+ mice underwent an aorto - caval fistula (ACF) or sham surgery and were subjected to echocardiographic examination at 2 wks. Mean arterial pressure (MAP) and atrial, left ventricular (LV) and right ventricular (RV) mass were greater in sham - operated ANP-/-mice than in ANP+/+mice. MAP decreased following ACF to a similar extent in both genotypes. ACF induced significant concentric cardiac enlargement in both genotypes. Cardiac enlargement and lung weight increased to a greater extent in ANP - / - mice than in ANP+/ + mice, indicating that disrupted ANP statement worsens ACF- induced cardiac enlargement and pulmonary congestion. LV function (velocity of circumferential shortening [VCFr], circumferential stress, fraction shortening, fraction shortening, and e-jection time and fraction) assessed by echocardiography did not differ between sham - operated ANP + / + and ANP - / - mice and remained unchanged after ACF. These findings indicate that ANP deletion results in biventricular enlargement and an exaggerated response to the stress of volume overload. This support the hypothesis that ANP has direct antihypertrophic and car-dioprotective actions in heart. Further study is needed to dissect the contributions of increased afterload from those of removing the antihypertrophic effects of ANP to basal and stress induced cardiac enlargement in this animal model.
基金Supported by National Natural Science Foundation of China,No.10672103 and 30360031
文摘AIM:To investigate atrial natriuretic peptide(ANP) secretion from gastric mucosa and the relationship between the ANP/natriuretic peptide receptor type A (NPR-A)pathway and diabetic gastroparesis. METHODS:Male imprinting control region(ICR)mice (4 wk old)were divided into two groups:control mice, and streptozotocin-induced diabetic mice.Eight weeks after injection,spontaneous gastric contraction was recorded by using physiography in control and streptozotocin-induced diabetic mice.The ANP-positive cells in gastric mucosa and among dispersed gastric epithelial cells were detected by using immunohistochemistry and flow cytometry,respectively.ANP and natriureticpeptide receptor type A(NPR-A)gene expression in gastric tissue was observed by using the reverse transcriptase polymerase chain reaction. RESULTS:The frequency of spontaneous gastric contraction was reduced from 12.9±0.8 cycles/min in the control group to 8.4±0.6 cycles/min in the diabetic mice(n=8,P<0.05).However,the amplitude of contraction was not significantly affected in the diabetic group.The depletion of interstitial cells of Cajal in the gastric muscle layer was observed in the diabetic mice.ANP-positive cells were distributed in the gastric mucosal layer and the density index of ANP-positive cells was increased from 20.9±2.2 cells/field in control mice to 51.8±2.9 cells/field in diabetic mice(n=8, P<0.05).The percentage of ANP-positive cells among the dispersed gastric epithelial cells was increased from 10.0%±0.9%in the control mice to 41.2%± 1.0%in the diabetic mice(n=3,P<0.05).ANP and NPR-A genes were both expressed in mouse stomach, and the expression was significantly increased in the diabetic mice. CONCLUSION:These results suggest that the ANP/ NPR-A signaling pathway is upregulated in streptozotocin-induced diabetic mice,and contributes to the development of diabetic gastroparesis.
基金supported by a grant from the National Natural Science Foundation of China(30260032.81000073 and 81160020)Key Program of Science and Technology of Hainan Province(061011 and ZDXM20100045)+2 种基金Education Department of Hainan Province(Hj2007113)Natural Science Foundation of Hainan Province(310043 and 811197)Key Project of Chinese Ministry of Education(212137) and HJHZ2013-06
文摘Objective:To understand the role of ANP mRNA transcription regulation in gpl30-mediated cardiomyocyte hypertrophy,and the involved mitogen-aetivated protein kinase kinase(MEK)-extracellular signal-regulated kinase(ERK,also called p42/p44 MAPK)signaling pathway.Methods:isolated neonatal ventricular myocytes were treated with different concentrations of CT-1(10^(-9),10^(-8)and 10^(-7)mol/L).MTT was used to analyze the viability and RT-PCR was used to detect ANP mRNA levels in eardiomyocyte.To inhibit p42/p44 MAPK activity in hypertrophic cardiomyoeytes,the cells were pretreated with a specific MEKI inhibitor.Results:CT-1significantly induced ANP mRNA expression and the viability of canliomyocytes in a doseand time-dependent manner.Furthermore,blocking p42/p44 MAPK activity by the special MEk1 inhibitor uprcgulatcd the ANP mKNA.Conclusions:p42/p44 MAPK have an important role in suppressing ANP mRNA transcription and cell activity in gpl30-mediated hypertrophic ventricular myocytes.
文摘AIM: To evaluate the value of plasma N-terminal pro- brain natriuretic peptide (NT-proBNP) level for predicting postoperative atrial fibrillation (AF) in patients undergoing surgery for esophageal carcinoma. METHODS: NT-proBNP levels were measured in 142 patients 24 h before and 1 h after surgery for esophageal carcinoma. All patients having a preoperative cardiac diagnosis by electrocardiogram (ECG), remained under continuous monitoring for at least 48 h after surgery, and then underwent clinical cardiac evaluation until discharge. RESULTS: Postoperative AF occurred in 11 patients (7.7%). AF patients were significantly older (69.6 ± 12.2 years vs 63.4 ± 13.3 years, P = 0.031) than non-AF patients. There were no significant differences in history of diabetes mellitus, sex distribution, surgical approach, anastomosis site, intraoperative hypotension and postoperative fever. The preoperative plasma NT-proBNP level was significantly higher in patients who developed postoperative AF (121.3 ± 18.3 pg/mL vs 396.1 ± 42.6 pg/mL, P = 0.016). After adjustment for age, gender, chronic obstructive pulmonary disease (COPD), history of cardiac diseases, hypertension, postoperative hypoxia and thoracic-gastric dilation, NT-proBNP levels were found to be associated with the highest risk factor for postoperative AF (odds ratio = 4.711, 95% CI = 1.212 to 7.644, P = 0.008).CONCLUSION: An elevated perioperative plasma BNP level is a strong and independent predictor of postoperative AF in patients undergoing surgery for esophageal carcinoma. This finding has important implications for identifying patients at higher risk of postoperative AF who should be considered for preventive antiarrhythmic therapy.
文摘BACKGROUND The prevalence of cardiovascular diseases,especially heart failure,continues to rise worldwide.In heart failure,increasing levels of circulating atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP)are associated with a worsening of heart failure and a poor prognosis.AIM To test whether a high concentration of BNP would inhibit relaxation to ANP.METHODS Pulmonary arteries were dissected from disease-free areas of lung resection,as well as pulmonary artery rings of internal diameter 2.5–3.5 mm and 2 mm long,were prepared.Pulmonary artery rings were mounted in a multiwire myograph,and a basal tension of 1.61gf was applied.After equilibration for 60 min,rings were pre-constricted with 11.21μmol/L PGF2α(EC80),and concentration response curves were constructed to vasodilators by cumulative addition to the myograph chambers.RESULTS Although both ANP and BNP were found to vasodilate the pulmonary vessels,ANP is more potent than BNP.pEC50 of ANP and BNP were 8.96±0.21 and 7.54±0.18,respectively,and the maximum efficacy(Emax)for ANP and BNP was-2.03 gf and-0.24 gf,respectively.After addition of BNP,the Emax of ANP reduced from-0.96gf to-0.675gf(P=0.28).CONCLUSION BNP could be acting as a partial agonist in small human pulmonary arteries,and inhibits relaxation to ANP.Elevated levels of circulating BNP could be responsible for the worsening of decompensated heart failure.This finding could also explain the disappointing results seen in clinical trials of ANP and BNP analogues for the treatment of heart failure.
文摘AIM: To evaluate the effect of ANP on warm I/R injury in a porcine THVE model. METHODS: Miniature pigs (mini-pigs) weighing 16-24 kg were observed for 120 min after reperfusion following 120 min of THVE. The animals were divided into two groups. ANP (0.1 μg/kg per min) was administered to the ANP group (n = 7), and vehicle was administered to the control group (n = 7). Either vehicle or ANP was intravenously administered from 30 min before the THVE to the end of the experiment. Arterial blood was collected to measure AST, LDH, and TNF-α. Hepatic tissue blood ? ow (HTBF) was also measured. Liver specimens were harvested for p38 MAPK analysis and histological study. Those results were compared between the two groups. RESULTS: The AST and LDH levels were lower in the ANP group than in the control group; the AST levels were signifi cantly different between the two groups (60 min: 568.7 ± 113.3 vs 321.6 ± 60.1, P = 0.038 < 0.05, 120 min: 673.6 ± 148.2 vs 281.1 ± 44.8, P = 0.004 < 0.01). No signifi cant difference was observed in the TNF-α levels between the two groups. HTBF was higher in the ANP group, but the difference was not signif icant. A signifi cantly higher level of phosphorylated p38 MAPK was observed in the ANP group compared to the controlgroup (0 min: 2.92 ± 1.1 vs 6.38 ± 1.1, P = 0.011 < 0.05).Histological tissue damage was milder in the ANP group than in the control group. CONCLUSION: Our results show that ANP has a protective role in I/R injury with p38 MAPK activation in a porcine THVE model.
文摘The present study investigated a possible mechanism for endogenous endothelin-1 (ET-1) regulation of atrial natriuretic peptide (ANP) secretion in isolated perfused acute hypoxic rabbit atria. Acute hypoxia significantly enhanced the release of ET-1 and the expression of the ET receptor (ETR) type A and B (ETR<sub>A</sub> and ETR<sub>B</sub>) in atrial tissues, with a concomitant increase in ANP secretion. The ETR<sub>A</sub> or ETR<sub>B</sub> antagonist, BQ123 (0.3 μmol/L) or BQ788 (0.3 μmol/L), respectively attenuated hypoxia-induced ANP secretion. Both antagonists significantly attenuated the levels of hypoxiainduced atrial phosphorylated (p)-extracellular signal-regulated kinase (ERK) and p-protein kinase B (Akt). The ERK and Akt inhibitors, PD098059 (30 μmol/L) and LY294002 (30 μmol/L), respectively mimicked the effect of the ETR antagonists. These results demonstrated that acute hypoxia- mediated atrial ET-1 regulated ANP secretion through ETR and the subsequent mitogenactivated protein kinase (MAPK)/ERK and ETR-phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathways. These pathways may mediate atrial endocrine functions under hypoxic conditions.
基金The authors gratefully acknowledge the support of this work by the National Natural Science Foundation of China(based on the Systems Biology of Acupuncture on Irritable Early Hypertension Control Mechanism and Intervention Study Targets Research,no.81072861).
文摘Objective:To explore the protective effect of acupuncture against myocardial injury in rats with stress-induced prehypertension (SIPH) by observing the genetic expression of myocardial endothelin-1 (ET-1) and atrial natriuretic peptide (ANP).Methods:Thirty-six Wistar rats were randomized into three groups:the control group,model group,and model + acupuncture (AP) group (n =12 rats per group).During the 11-day modeling period,the model group and the model + AP group experienced plantar electric stimulation in combination with noise exposure,and daily acupuncture intervention was applied simultaneously in the model + AP group;the control group did not experience modeling or acupuncture.Systolic pressure (SP) was measured the day before modeling began,and on the 3rd,5th,7th,9th,and 11th day after modeling initiation.On the 12th day,histopathological observation of the left ventricle was made with hematoxylin-eosin staining and quantitative genetic expression of myocardial ET-1,and ANP was tested by quantitative real-time polymerase chain reaction (PCR).Results:SP was higher in the model group than the control group on the 3rd,5th,7th,9th,and 11th days (all P <.01).SP in the model + AP group was lower than that in the control group on the 5th and 7th days (respectively,P =.008,P =.002) and on the 9th and 11th days (P =.029,P =.039).Hematoxylin-eosin staining showed normal myocardial cellular structure in the control group.The model group showed disordered arrangement of cardiac cells with morphological changes in some nuclei,including enlargement or dissolution;there was also infiltration of inflammatory cells and proliferation of collagen fibers.In the model + AP group,most of the myocardial cells were normally structured,and only part of the cells had morphological changes with enlarged nuclei or dissolution.Real-time PCR showed that expression of ET-1 and ANP mRNA in the model group was greater than the control group (respectively,P =.024,P =.000101).The model + AP group had lower expression of ET-1 and ANP mRNA compared with the model group (respectively,P =.033,P =.043).Conclusion:Acupuncture may lower blood pressure and downregulate the genetic expression of myocardial ET-1 and ANP in SIPH rats,suggesting a protective effect of acupuncture against myocardial damage.
文摘Changes in plasma atrial natriuretic peptide(ANP)and serum lipids were observed us-ing dietetic atherosclerosis(AS)models.The results showed that plasma ANP level of the ASgroup was significantly higher than that of the control group(14.33±3.58μg/L vs 9.43±3.14μg/L).There was also a marked increase in serum Tch,TG,LDL-ch and VLDL-ch comparedwith the control group(P【0.01),suggesting that release of ANP increased with disturbance ofthe serum lipids and during AS formation,and that change in ANP was closely related to Tchand LDL-ch(P【0.05).Possible mechanisms causing these changes are also discussed.
文摘The effects of highly-potent atrial natriuretic peptide (HPANP) on circulating re nin-angiotensin-aldos-terone system (RAAS) and cardiac function were studied in an acute ischemic heart failure model. HPANP (6 μg/kg and 3 μg/kg) was infused intracoronarily. It was found that both doses of HPANP could cause significant decrease in plasma renin activity (PRA), angiotensin II (AII) and aldosterone (Ald). After the administraticn of HPANP, PRA, AII and Ald in the coronary sinus were decreased by 73. 2% (P<0.01), 68. o% (P<0.01) and 73. 6% (P<0.01), and the hormones in peripheral venous blood by 63. 3% (P<0.01), 53. 3% (P<0.01) and 64. 9% (P<0.01), respectively at the dose of 6 μg/kg. While PRA, AII and Ald in the coronary sinus and in peripheral venous blood decreased by 55. 9%, 55. 3%, 61. 9%, and 54. 0%, 42. 3%, 53, 3%, respectively at the 3μg/kg dose level. At the higher dose, HPANP increased left ventricular systolic pressure (LVSP, +13. 1%, P<0. 05), +dP/dtmax(+24.1 %, P<0.01), -dp/dtmax (+35.9%, P<0.01), and VCE(+28.9%, P<0.05). Mean arterial pressure and left ventricular end-diastolic pressure (LVEDP) were decreased (-15.0%, P<0.01, and 29. 6%, P<0.01, respectively). In contrast, the lower dose caused no significant changes of LVSP, +dp/dtmex,dp/dtmax and VCE(not including LVEDP, - 20. 5 %, P<0.05). Neither of the doses caused significant changes in heart rate and T value- Normal saline infusion has no effects on cardiac function and circulating RAAS- We conclude that in ischemic heart failure, intracoronary administration of HPANP can significantly suppress the activity of circulating RAAS, and improve cardiac function by reducing pre- and after-load of the heart, but has no direct myocardial effects.
文摘Background: Sex dimorphism in the prevalence, onset, development and progression of cardiovascular disease (CVD) is well recognized, but the mechanisms whereby sex hormones are believed to confer cardioprotection are still not fully understood. Objective: This study more closely delineates the effect of 17β-Estradiol (E2) on the expression and signaling of the cardiac NP and NOS systems, well-known cardioprotective modulators of the cardiac hypertrophy (CH) response, that both contribute to downstream production of cyclic guanosine 3’,5’-monophosphate (cGMP). Materials and Methods: Ovariectomized (OVX) female ANP+/+ and ANP-/- mice, 6 - 7 weeks old, were subjected to a five-week treatment with E2 (100 μg/100 μL/day) or vehicle (VEH). Left ventricle from these treatment groups, along with that from age-matched male ANP+/+ and ANP-/- mice was used to assess expression of these systems by real-time quantitative PCR (qPCR). Left ventricle tissue and plasma cGMP were measured by enzyme immunoassay to assess alterations in resultant downstream signaling. Results: NP system expression was unchanged across genotype, sex and E2 treatment. Sex-specific differences in NOS system expression were observed;female mice showed an increased expression of NOS system genes that were significantly elevated in all but one of the E2 treatment groups. Left ventricle tissue cGMP remained unchanged across genotype, sex and E2 treatment. Plasma cGMP levels were unchanged in ANP+/+ treatment groups. In ANP-/- treatment groups, plasma cGMP in the female OVX-E2 mice was significantly higher compared to male and female OVX-VEH mice. Conclusion: These findings demonstrate that in the absence of ANP, E2 upregulates cardiac NOS system expression to produce cGMP. This study confirms the importance of the cardiac NOS system in females;this particular system may be a promising future target for sex-specific treatments and therapies for CVD in women.
文摘Objectives To investigate the possible role of amino-terminal pro-brain natriuretic peptide (NT-proBNP) in the occurrence of atrial fibrillation (AF) after coronary artery bypass grafting (CABG). Methods This study group included 70 consecutive patients scheduled for elective off-pump CABG. The patients with ejection fraction (EF) less than 0. 30, history of AF, use of class Ⅰ or Ⅲ antiarrhythmic drug, implanted pacemaker, postoperative myocardial infarction or chest reopening for pericardial tamponade were excluded. Preoperative and postoperative serum NT-proBNP levels were measured by radioimmunoassay technique. Results Postoperative AF occurred in 15 patients (21.4%); these patients had significantly higher median NT-proBNP levels when compared with those without AF after the operation ( P 〈 0. 01 ). Using multivariate logistic regression analyses, an increase in NT-proBNP level after CABG was found to be independently associated with AF ( OR = 3.78, 95% IC = 1.81 - 4. 89, P 〈 0. 01 ). Increased age, diabetes mellitus, preoperative use of β-blocker, proximal right coronary artery involvement, and longer operation time were al- so associated with AF. Conclusions These results indicated that AF was associated with higher NT-proBNP concentrations after off pump CABG; the increase in NT-proBNP after CABG may play an important role in the occurrence of AF after the operation. The further studies are needed to define the reason that lead to higher NT-proBNP concentrations among the patients who present AF after off pump CABG.
文摘BACKGROUND Natriuretic peptides are involved in the cascade of pathophysiological events occurring in liver cirrhosis,counterbalancing vasoconstriction and anti-natriuretic factors.The effects of natriuretic peptides as treatment of cirrhotic ascites have been investigated only in small studies,and definitive results are lacking.AIM To examine the effects and safety of natriuretic peptides in cirrhosis patients with ascites.METHODS We searched MEDLINE,Web of Science,Scopus,Cochrane Library and Embase for all available studies applying intravenous administration of any natriuretic peptide to patients suffering from cirrhotic ascites.Inclusion was not limited by treatment duration or dose,or by follow-up duration.Both randomised controlled trials and non-randomised studies were eligible for inclusion.The primary outcome was change in renal sodium excretion.Secondary outcomes included safety measures and changes in renal water excretion,plasma aldosterone concentration,and plasma renin activity.RESULTS Twenty-two studies were included.Atrial natriuretic peptide(ANP)was the only intensively studied treatment.Sodium excretion increased in response to continuous ANP infusion and was more pronounced when infusion rates of>30 ng/kg/min were administered compared with≤30 ng/kg/min(P<0.01).Moreover,natriuresis was significantly higher in study subgroups with mild/moderate ascites compared with moderate/severe and refractory ascites(P<0.01).ANP infusions increased renal water excretion,although without reaching a statistically significant dose-response gradient.Plasma aldosterone concentration and plasma renin activity were significantly lower at baseline in study subgroups achieving a negative sodium balance in response to an ANP administration compared with treatment non-responders(P<0.01).Blood pressure decreases occurred less frequently when ANP doses≤30 ng/kg/min were applied.The quality of evidence for a natriuretic response to ANP was low,mainly due to small sample sizes and considerable between-study heterogeneity.Data were sparse for the other natriuretic peptides;B-type natriuretic peptide and urodilatin.CONCLUSION Intravenous ANP infusions increase sodium excretion in patients with cirrhotic ascites.Continuous infusion rates>30 ng/kg/min are the most effective.However,safety increases with infusion rates≤30 ng/kg/min.
文摘Aims: To characterize the plasma levels of the atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in patients with atrioventricular nodal reentry tachycardia (AVNRT), we measured the plasma levels of these peptides before and during tachycardia. Methods: We included 10 consecutive patients scheduled for ablation of typical AVNRT without structural heart disease. Catheters were inserted in the femoral artery, femoral vein, and coronary sinus (CS) prior to the ablation procedure. Blood samples were drawn before and after 3 min of tachycardia to measure plasma levels of ANP and BNP. Right atrial pressure (RAP) was measured at baseline. Results: Of the 10 patients, in three patients it was not possible to induce tachycardia leaving a total of 7 patients available for analysis. Mean age of the seven included patients was 40 ± 12 years (mean ± SD), five were female. ANP levels increased significantly during tachycardia in the artery (p = 0.0009) and vein (p = 0.003), but only borderline in CS (p = 0.09). BNP levels did not change during tachycardia in any location. Conclusion: ANP levels measured in the peripheral circulation increased acutely during tachycardia due to AVNRT. BNP levels did not increase.
文摘Compared to their linear counterparts,cyclic peptides show better biological activities,such as antibacterial,immunosuppressive,and anti-tumor activities,and pharmaceutical properties due to their conformational rigidity.However,cyclic peptides could form numerous putative metabolites from potential hydrolytic cleavages and their fragments are very difficult to interpret.These characteristics pose a great challenge when analyzing metabolites of cyclic peptides by mass spectrometry.This study was to assess and apply a software-aided analytical workflow for the detection and structural characterization of cyclic peptide metabolites.Insulin and atrial natriuretic peptide(ANP)as model cyclic peptides were incubated with trypsin/chymotrypsin and/or rat liver S9,followed by data acquisition using TripleTOF?5600.Resultant full-scan MS and MS/MS datasets were automatically processed through a combination of targeted and untargeted peak finding strategies.MS/MS spectra of predicted metabolites were interrogated against putative metabolite sequences,in light of a,b,y and internal fragment series.The resulting fragment assignments led to the confirmation and ranking of the metabolite sequences and identification of metabolic modification.As a result,29 metabolites with linear or cyclic structures were detected in the insulin incubation with the hydrolytic enzymes.Sequences of twenty insulin metabolites were further determined,which were consistent with the hydrolytic sites of these enzymes.In the same manner,multiple metabolites of insulin and ANP formed in rat liver S9 incubation were detected and structurally characterized,some of which have not been previously reported.The results demonstrated the utility of software-aided data processing tool in detection and identification of cyclic peptide metabolites.
基金This study was supported by grants from the National Natural Science Foundation of China (No. 30670928, No. 81070055), Beijing Educational Commission (No. PXM2011_014226 07 000060), Beijing Science and Technology Commission (No. Z111100074911001), Beijing Natural Science Foundation (No. 7112046, No. 7122056), Beijing Health System High Level Health Technical Personnel Training Plan (No. 2011-1-4).
文摘Background An inflammatory response leading to organ dysfunction and failure continues to be a major problem after injury in many clinical conditions such as sepsis, severe burns, and trauma. It is increasingly recognized that atrial natriuretic peptide (ANP) possesses a broad range of biological activities, including effects on endothelial function and inflammation. A recent study has revealed that ANP exerts anti-inflammatory effects. In this study we tested the effects of human ANP (hANP) on lung injury in a model of oleic acid (OA)-induced acute lung injury (ALl) in rats. Methods Rats were randomly assigned to three groups (n=6 in each group). Rats in the control group received a 0.9% solution of NaCI (1 ml-kg-l.h1) by continuous intravenous infusion, after 30 minutes a 0.9% solution of NaCI (1 ml/kg) was injected intravenously, and then the 0.9% NaCI infusion was restarted. Rats in the ALl group received a 0.9% NaCI solution (1 ml-kgl-h-~) intravenous infusion, after 30 minutes OA was injected intravenously (0.1 ml/kg), and then the 0.9% NaCI infusion was restarted. Rats in the hANP-treated ALl group received a hANP (0.1 IJg.kg-Lmin~) infusion, after 30 minutes OA was injected intravenously (0.1 ml/kg), and then the hANP infusion was restarted. The anti-inflammation effects of hANP were evaluated by histological examination and determination of serum cytokine levels. Results Serum interleukin (IL)-113, IL-6, IL-10 and tumor necrosis factor (TNF) a were increased in the ALl group at six hours. The levels of all factors were significantly lower in the hANP treated rats (P 〈0.005). Similarly, levels of IL-113, IL-6, IL-10 and TNF-a were higher in the lung tissue in the ALl group at six hours, hANP treatment significantly reduced the levels of these factors in the lungs (P 〈0.005). Histological examination revealed marked reduction in interstitial congestion, edema, and inflammation. Conclusion hANP can attenuate inflammation in OA-induced lung injury in rat model.
文摘Background Radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) has developed rapidly,and is a commonly performed ablation in many major hospitals throughout the world,due to its satisfactory results.The aim of this study was to detect the effect of RFCA on C-reactive protein (CRP),brain natriuretic peptide (BNP),and echocardiograph in patients with persistent and permanent AF.Methods A total of 120 patients (71 males,mean age (50.8&#177;12.0) years) with persistent and permanent AF undergoing RFCA under guidance of the Carto merge technique were studied.Left atrial diameter (LAD),right atrial diameter (RAD),left ventricular ejection fraction (LVEF),CRP,and BNP were observed 3,6 and 12 months after RFCA and compared with results before RFCA.The recurrence of atrial arrhythmias was observed 3 and 12 months after the procedure.Results Compared with that before RFCA,LAD and RAD decreased and LVEF increased significantly after RFCA.Meanwhile,the levels of CRP and BNP were reduced significantly at 3,6,and 12 months after RFCA (P〈0.05).In the non-recurrent patients,LVEF was increased significantly compared with the recurrent patients at 3,6,and 12 months after RFCA (P〈0.05).CRP and BNP levels were decreased significantly in the non-recurrent patients compared with the recurrent patients at 3,6,and 12 months after RFCA (P〈0.05).After one or two applications of RFCA,during a follow-up of 12 months,12 patients (10.0%) had AF,10 patients (8.3%) had atrial flutter,and 5 patients had atrial tachycardia (4.2%).Conclusions Conversion of AF to sinus rhythm by RFCA,has been shown to reduce LA size and improve LVEF.It can also significantly decrease the levels of CRP and BNP in patients with persistent and permanent AF and reduce the risk of inflammation and developing heart failure.