Gastric nNOS reduction accompanied by natriuretic peptides signaling pathway upregulation in diabetic mice

AIM: To investigate the relationship between neuronal nitric oxide synthase (nNOS) expression and the natriuretic peptide signaling pathway in the gastric fundus of streptozotocin (STZ)-induced diabetic mice.

Understanding heart failure in the elderly with respect to diastolic dysfunction and role for natriuretic peptides

The current issue of the Journal of Geriatric Cardiology contains an interesting paper by Dr. Yixin Song and colleagues raising important issues in the diagnosis and management of heart failure in elderly patients. Readers of this journal are in all likelihood aware that the epidemic of heart failure is of great impact medically and economically worldwide.

The Lebanese Society of Cardiology Consensus Statement on the Use of Natriuretic Peptides for the Management of Heart Failure

Plasma concentration of Natriuretic Peptide (NP) is a valuable diagnostic tool for heart failure (HF). It can help rule out or confirm a diagnosis of HF based on symptoms, but its use is not clearly defined. NPs should be used in conjunction with physical examination and other diagnostic tests. However, it is important to note that several conditions besides the diagnosis of HF may cause NPs levels to be elevated. Additionally, there are situations when NP concentrations may be below diagnostic thresholds in [1]. This consensus statement aims to provide a straightforward diagnostic flowchart for clinicians in both the emergency department and outpatient settings to aid in diagnosing both acute and chronic HF. The diagnosis of acute HF can be ruled out with a BNP level of 100 pg/mL or NTproBNP level of 300 pg/mL, regardless of the patient’s age. To identify HF, a 3-level cut-off point based on the patient’s age is recommended. Chronic heart failure can be ruled out with a BNP level of 35 pg/mL or NTproBNP level of 125 pg/mL, regardless of thepatient’s age [1].

Effects and safety of natriuretic peptides as treatment of cirrhotic ascites:A systematic review and meta-analysis

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.

Plasma natriuretic peptides during supraventricular tachycardia: A study in patients with atrioventricular nodal reentry tachycardia

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.

DISTRIBUTION AND LOCATION OF IMMUNOREACTIVE ATRIAL NATRIURETIC PEPTIDES IN COCHLEAR STRIA VASCULARIS OF GUINEA PIG

The distribution and location of atrial natriuretic peptides(ANP) in the cochlear stria vaseularis of normal guinea pigswere studied to find out regional regulating factors of cochlearblood flow (CBF) and productive foundation of cochlearendolymph by ABC immunocytochemistry and immunoele-ctronmicroscopy. The ANP-IR products were seen in the striavascularis of the 1-4 turns of the lateral wall of the cochlea,more markedly along its margin; and were negative in the spi-ral ligaments. Immunoelectronmicroscopically, a plenty ofsphericals of 250-350nm in diameter were noted in thecytoplasm of marginal and intermediate cells, but few in thebasal cells. The results suggest that the cochlear striavascularis had the function of secreting ANP in the guinea pig.

Utility of cardiac biomarkers in sports medicine:Focusing on troponin,natriuretic peptides,and hypoxanthine

Evidence-based consensus suggests that physical activity and regular exercise training can reduce modifiable risk factors as well as rate of mortality and morbidity in patients with chronic diseases,such as cardiovascular disease(CVD),diabetes,obesity and cancer.Conversely,long-term exercise training and drastic increase in vigorous physical activity may also cause acute cardiovascular events(e.g.acute myocardial infarction)and deleterious cardiac remodeling,particularly when exercise is performed by unfit or susceptible individuals.There is a reversed J-shaped hormesis-like curve between the duration and intensity of exercise and level of CVD risks.Therefore,it is important for an early detection of cardiac injuries in professional and amateur athletes.Under this context,this article focuses on the use of biomarker testing,an indispensable component in the current clinical practices especially in Cardiology and Oncology.We attempt to justify the importance of using circulating biomarkers in routine practices of Sports Medicine for an objective assessment of CVD events following exercise.Special attentions are dedicated to three established or emerging cardiac biomarkers(i.e.cardiac troponins,natriuretic peptides,hypoxanthine)for myocardial tissue hypoxia/ischemia events,muscle stress,and the consequent cellular necrotic injury.Based on these focused analyses,we propose use of circulating biomarker testing in both laboratory and point-of-care settings with an increasingly broader involvement or participation of team physicians,trainers,coaches,primary care doctors,as well as educated athlete community.This diagnostic approach may improve the quality of medical surveillance and preventive measures on exercise-related CVD risks/outcomes.

Regulation of C-type Natriuretic Peptides and Natriuretic Peptide Receptor-B Expression in Diabetic Rats Renal Treated by Tongluo Recipe(通络方)

To investigate the expression of C-type natriuretic peptides （CNP） and natriuretic peptide receptor-B （NPR-B） receptor in diabetic rats renal cortex, and the regulation by Tongluo Recipe （通络方, TLR）. Methods： Sixty male SD rats were divided into 3 groups： the normal control group, diabetic model group and diabetic TLR group. Each group was further divided into two subgroups of ten in each, according to 4-week or 12-week observation period. Streptozotocin （STZ）-induced diabetic rats were treated with TLR （1.0 g.kgl＇d1） for 4 and 12 weeks, respectively. （1） The essential information was collected for comparing renal mass, serum creatinine and 24 h urine albumen on each group was calculated. （2） CNP mRNA and NPR-B mRNA were detected by realtime-polymerase chain reaction （PCR） on rats renal cortex. （3） Concentration of CNP on renal cortex or serum were analyzed by enzyme-linked immunosorbent assay （ELISA）. （4） Pathological evaluation and NPR-B immunostaining for renal tissue were also performed. Results： （1） CNP and NPR-B mRNA levels were detected in each treated or untreated group, with slight elevated in untreated diabetes rats administrated with STZ after 4-week and CNP mRNA level remarkable elevated at 39.21 times higher than normal control group after 12 weeks, but NPR-B mRNA level showed a remarkably down-regulation at 98.07% after 12 weeks. CNP mRNA of TLR-treated group was also elevated after 12-week treatment, but less than untreated group. （2） Concentrations of CNP in renal cortex were obviously increased in treated or untreated diabetes rats, within these groups the treatment of TLR was found more significantly on prompting CNP concentration. Comparing to normal group, serum concentrations of CNP were also increased in treated or untreated diabetic groups, but there was no difference between these diabetic groups. （3） Renal lesions like glomerular volume increased are observed mostly in the relative eady stage after 4 weeks. Although TLR treated group had no significant difference in their glomerular volume, the degrees of injury of glomerulus were ameliorated, as well as the NPR-B immunostaining enhanced in glomerulus. Weakly positive immunostaining of NPR-B are observed in glomerulus of normal control, and negative in glomerulus of untreated diabetes rats administrated with STZ after 12 weeks, whereas TLR-treatment groups showed a little enhancement. Conclusion： CNP and NPR-B showed different characteristic on renal cortex at different pathological period in diabetes rats, and TLR regulated their expression.

Comprehensive effects of traditional Chinese medicine treatment on heart failure and changes in B-type natriuretic peptide levels: A meta-analysis

BACKGROUND Heart failure(HF),a common cardiovascular condition,is characterized by significant morbidity and mortality.While traditional Chinese medicine(TCM)is often used as a complementary approach in HF management,systematic evalua-tions of its impact on clinical outcomes,TCM syndrome scores,and B-type natriuretic peptide(BNP)levels are lacking.This study fills this gap through a comprehensive analysis of randomized controlled trials(RCTs)focusing on TCM for HF treatment.It encompasses an assessment of methodological quality,a meta-analysis,and an evaluation of evidence quality based on established standards.The results offer crucial insights into the potential advantages and constraints of TCM in HF management.RCTs on TCM for HF treatment published since the establishment of the database were searched in four Chinese and English databases,including China National Knowledge Infrastructure,Wanfang,VIP Information Chinese Science and Technology Journal,and PubMed.Methodological quality was assessed for the included studies with the Cochrane risk-of-bias assessment tool,and the meta-analysis and publication bias assessment was performed with the RevMan5.3 software.Finally,the quality of evidence was rated according to the GRADE criteria.RESULTS A total of 1098 RCTs were initially retrieved.After screening,16 RCTs were finally included in our study,which were published between 2020 and 2023.These RCTs involved 1660 HF patients,including 832 in the TCM group[TCM combined with conventional Western medicine(CMW)treatment]and 828 in the CWM group(CWM treatment).The course of treatments varied from 1 wk to 3 months.TCM syndrome differentiation was analyzed in 11 of the included RCTs.In all included RCTs,outcome indicators included comprehensive clinical outcomes,TCM syndrome scores,and BNP levels.The meta-analysis results showed significant differences between the TCM and CWM groups in terms of comprehensive clinical outcomes[risk ratio=-0.54;95%confidence interval(CI)=-0.61,-0.47;P<0.00001],TCM syndrome scores[weighted mean difference(WMD)=-142.07;95%CI=-147.56,-136.57;P<0.00001],and BNP levels(WMD=-142.07;95%CI=-147.56,-136.57;P<0.00001).According to the GRADE criteria,RCTs where"TCM improves clinical comprehensive outcomes"were rated as low-quality evidence,and RCTs where"TCM reduces TCM syndrome scores"or"TCM decreases BNP levels"were rated as medium-quality evidence.CONCLUSION TCM combined with CWM treatment effectively improves comprehensive clinical outcomes and diminishes TCM syndrome scores and BNP levels in HF patients.Given the low and medium quality of the included RCTs,the application of these results should be cautious.

Effect Study of the Recombinant Human Brain Natriuretic Peptide in Patients with Heart Failure Combined with Hypotension

Objective: This paper aims to investigate the effect of applying recombinant human brain natriuretic peptide in patients with heart failure combined with hypotension. Recombinant human brain natriuretic peptide is a synthetic polypeptide drug that is primarily used to treat acute heart failure. Its mechanism of action closely mimics that of human endogenous brain natriuretic peptide. By binding to receptors on cardiomyocytes, it exerts its pharmacological effects. Methods: For the study, 76 heart failure patients with hypotension were selected from our hospital between May 2022 and June 2023. These patients were divided into two groups: a control group and an observation group, each comprising 38 patients. The control group received dopamine treatment, while the observation group was treated with recombinant brain natriuretic peptide. The objective was to compare the effects of the treatments in both groups by analyzing cardiac function indices and levels of vasoactive substances to identify any significant differences in outcomes. Results: The overall response rate of the patients in the observation group and the control group was 94.74% and 73.68%, significantly higher as compared with the observation group (P 0.05). After the following treatment, BNP, ANNP and urine output in the observation group were significantly different compared with the control group, of the statistical significance (P Conclusion: For the treatment of heart failure patients with hypotension, the clinical application of recombinant human brain natriuretic peptide is the most ideal, and significantly improves the cardiac function of patients, which is worth popularizing.

Increased N-terminal pro-brain natriuretic peptide level predicts atrial fibrillation after surgery for esophageal carcinoma

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.

Comparative study of galectin-3 and B-type natriuretic peptide as biomarkers for the diagnosis of heart failure

Background Heart failure （HF） is a common disease with complex pathophysiological causes. The diagnosis of HF commonly relies on comprehensive analyses of medical history and symptoms, and results from echocardiography and biochemical tests. Galectin-3, a rela-tively new biomarker in HF, was approved by the US Food and Drug Administration in 2010 as a marker in the stratification of risk for HF. We assessed galectin-3 as a biomarker for HF diagnosis in patients with preserved ejection fraction （pEF） and compared its performance with that of B-type natriuretic peptide （BNP）. Methods Thirty-five pEF patients with HF （HFpEF group） and 43 pEF patients without HF （control group） were enrolled. Plasma levels of galectin-3 and BNP in HFpEF and control subjects were determined. Sensitivity, specificity, pre dictive values, and accuracy of galectin-3 and BNP as markers for HF diagnosis were calculated and compared. Results Levels of galec- tin-3 and BNP were 23.09 ±6.97 ng/mL and 270.46 ± 330.41 pg/mL in the HFpEF group, and 16.74 ± 2.75 ng/mL and 59.94 ± 29.93 pg/mL in the control group, respectively. Differences in levels of galectin-3 and BNP between the two groups were significant （P 〈 0.01）. As a bio- marker for HF diagnosis in study subjects, galectin-3 showed sensitivity and specificity of 94.3% and 65.1%, respectively, at a cutoff value of 17.8 ug/mL. BNP showed sensitivity and specificity of 77.1% and 90.7%, respectively, at a cutoff value of 100 pg/mL. Galectin-3 was a significantly more sensitive （P 〈 0.05） but less specific （P 〈 0.01） biomarker compared with BNP. Differences in positive predictive value, negative predictive value, and accuracy between galectin-3 and BNP markers were not significant （P 〉 0.05）. Areas under the receiver operating characteristic curve （95% confidence interval） were 0.891 （0.808-0.974） and 0.896 （0.809-0.984） for galectin-3 and BNP, respec- tively, with no significant difference between the two values （P 〉 0.05）. Conclusions The level of galectin-3 is significantly elevated in patients with HF. Galectin-3 and BNP are useful biomarkers for the diagnosis of HF in patients with pEF.

C-type natriuretic-peptide-potentiated relaxation response of gastric smooth muscle in streptozotocin-induced diabetic rats

AIM: To study the sensitivity of gastric smooth muscle to C-type natriuretic peptide (CNP) in streptozotocin (STZ)-induced diabetic rats. METHODS: The spontaneous contraction of a gastric smooth muscle strip was recorded by using physiological methods in rats. The expressions of CNP and natriuretic peptide receptor-B (NPR-B) in gastric tissue were examined by using immunohistochemistry techniques in the diabetic rat. RESULTS: At 4 wk after injection of STZ and vehicle, the frequency of spontaneous contraction of gastric smooth muscle was significantly reduced in diabetic rats, and the frequency was decreased from 3.10 ± 0.14 cycle/min in controls to 2.23 ± 0.13 cycle/min (n = 8, P < 0.01). However, the amplitude of spontaneous contraction was not significant different from the normal rat. CNP significantly inhibited spontaneous contraction of gastric smooth muscle in normal and diabetic rats, but the inhibitory effect was significantly potentiated in the diabetic rats. The amplitudes of spontaneous contraction were suppressed by 75.15% ± 0.71% and 58.92% ± 1.32% while the frequencies were decreased by 53.33% ± 2.03% and 26.95% ± 2.82% in diabetic and normal rats, respectively (n = 8, P < 0.01). The expression of CNP in gastric tissue was not changed in diabetic rats, however the expression of NPR-B was significantly increased in diabetic rats, and the staining indexes of NPR-B were 30.67 ± 1.59 and 17.63 ± 1.49 in diabetic and normal rat, respectively (n = 8, P < 0.01).CONCLUSION: The results suggest that CNP induced an inhibitory effect on spontaneous contraction of gastric smooth muscle, potentiated in diabetic rat via up-regulation of the natriuretic peptides-NPR-B-particulate guanylyl cyclase-cyclic GMP signal pathway.

The role of C-type natriuretic peptide in rat testes during spermatogenesis

C-type natriuretic peptide （CNP） is a 22-amino acid peptide and act as a local paracrine or autocrine regulator. There is growing evidence that ChIP is involved in male reproductive processes. To investigate the role of CNPduring spermatogenesis, we measured the mRNA expression of CNPand its specific membrane-bound natriuretic peptide receptor-B （NPR-B） using real-time RT-PCR in the testes of normal rats on different postnatal days. After that spermatogenesis dysfunction model induced by ornidazole was established with the aim to study the correlation of CNPwith spermatogenic dysfunction. Then, Sertoli cells from 18- to 22-day-old healthy male rats were cultured in the presence of different CNPconcentrations （1 ×10-6, 1×10-7 and1×10-8 mol l-1）, and the mRNA expression levels of androgen.binding protein, inhibin B and transferrin were examined at 0 min, 30 min, 1 h, 2 h, 4 h, 8 h, 12 h, 24 h and 48 h. During the postnatal development of rat testes, the highest mRNA expression levels of CNPand NPR-B were found at postnatal Do, and the levels then declined gradually, with a second ChIPpeak at postnatal D35. In the ornidazole-induced infertile rat testes, CIVPgene expression was lower than in the uninduced rats （P〈0.05）, while IVPR-Bgene expression was greater （P〈0.05）. In cultured Sertoli cells, supplementation with CNP stimulated the gene expression of androgen-binding pmteirginhibin B/transferrin, particularly at 12 h, and 1× 10-7 mol l-1 CNP had the highest upregulation effect. The gene expression levels of CNPIIVPR-B in rat testes at different postnatal stages and in infertile rat testes indicated that CNP may participate in the physiology and/or pathology related to spermatogenesis. Moreover, ChIP regulated endocrine function in Sertoli cells. Taken together, these results showed that CNP is closely tied to spermatogenesis.

Plasma brain natriuretic peptide, platelet parameters, and cardiopulmonary function in chronic obstructive pulmonary disease

BACKGROUND Chronic obstructive pulmonary disease(COPD)is a chronic respiratory disease with worldwide occurrence and high disability and mortality rate.It occurs mostly in the elderly population with pulmonary heart disease,type II respiratory failure,and other serious complications.AIM To investigate the correlation of plasma brain natriuretic peptide(BNP)and platelet parameters with cardiac function and pulmonary hypertension in patients with COPD and pulmonary heart disease.METHODS From June 2016 to June 2019,52 patients with COPD-pulmonary heart disease(pulmonary heart disease group),30 patients with COPD(COPD group),and 30 healthy individuals(control group)in our hospital were enrolled in the study.The pulmonary heart disease group was further divided into subgroups according to cardiac function classification and pulmonary artery pressure.Plasma BNP and platelet parameters were estimated and compared among each group and subgroup.The correlation of plasma BNP and platelet parameters with cardiac function classification and pulmonary artery pressure was then analyzed.RESULTS In the pulmonary heart disease group,the COPD group,and the control group,the levels of plasma BNP,platelet distribution width(PDW),and mean platelet volume(MPV)showed a decreasing trend(P<0.05),while an increasing trend was found in platelet count(PLT)and plateletcrit(PCT)levels among the three groups(P<0.05).In the pulmonary hypertension mild,moderate,and severe subgroups,the levels of plasma BNP,PDW,and MPV showed an increasing trend(P<0.05),while a decreasing trend was observed in PLT levels(P<0.05);however,PCT levels showed no significant difference among the three subgroups(P>0.05).In the cardiac function grade I,II,III,and IV subgroups,the levels of plasma BNP,PDW,and MPV showed an increasing trend(P<0.05),while a decreasing trend was noted in PLT and PCT levels among the four subgroups(P<0.05).Correlation analysis showed that the levels of plasma BNP,PDW,and MPV in patients with pulmonary heart disease were positively correlated with their pulmonary artery pressure(P<0.05),while PLT was negatively correlated with their pulmonary artery pressure(P<0.05).Moreover,plasma BNP,PDW,and MPV levels were positively correlated with cardiac function grade(P<0.05)of these patients,while PLT and PCT levels were negatively correlated with their cardiac function grade(P<0.05).CONCLUSION Plasma BNP and PLT parameters are significantly correlated with the cardiac function and pulmonary hypertension in patients with COPD and pulmonary heart disease,indicating that these parameters have high clinical relevance in reflecting the health condition of these patients and for guiding their treatment.

Marked elevation of B-type natriuretic peptide in patients with heart failure and preserved ejection fraction

Marked elevations of B-type natriuretic peptide （BNP） are not generally seen in patients with heart failure and preserved ejection fraction （HFpEF）. The objective of this study was to examine the clinical and laboratory characteristics of a large cohort of patients with HFpEF and markedly elevated BNP. A retrospective examination of 421 inpatients at a university hospital admitted with a diagnosis of HFpEF was performed. Clinical and echocardiographic data in 4 groups of patients with levels of BNP ≤ 100 pg/mL, 100-400 pg/mL, 400-1,000 pg/mL and 〉 1,000 pg/mL were compared. Patients with HFpEF and BNP 〉 1,000 pg/mL （28% of the population） were characterized by impaired renal function and greater use of anti-hypertensive medications. A subset of these patients with BNP 〉 1,000 pg/mL had normal renal function （21%） and were significantly older, more frequently female, and tended to have lower ejection fractions. Conversely, patients with HFpEF and BNP ≤100 pg/mL were younger and had preserved renal function. BNP was inversely related to the likelihood of subsequent admission for heart failure, but not to myocardial infarction or death. In conclusion： BNP 〉 1,000 pg/mL is seen in almost 1/3 of patients hospitalized with HFpEF. This elevation of BNP often reflects impaired renal function, but can also be seen in patients with preserved renal function but relatively impaired systolic function.

Brain natriuretic peptide is a potent vasodilator in aged human microcircula- tion and shows a blunted response in heart failure patients

Background Brain natriuretic peptide （BNP） is normally present in low levels in the circulation, but it is elevated in parallel with the degree of congestion in heart failure subjects （CHF）. BNP has natriuretic effects and is a potent vasodilator. It is suggested that BNP could be a therapeutic alternative in CHF. However, we postulated that the high levels of circulating BNP in CHF may downregulate the response of microvascular natriuretic receptors. This was tested by comparing 15 CHF patients （BNP 〉 3000 ng/L） with 10 matched, healthy controls. Methods Cutaneous microvascular blood flow in the forearm was measured by laser Doppler Flowmetry. Local heating （＋44°C, 10 min） was used to evoke a maximum local dilator response. Results Non-invasive iontophoretic administration of either BNP or acetylcholine （ACh）, a known endothelium-dependent dilator, elicited an increase in local flow. The nitric oxide synthase inhibitor, l-N-Arginine- methyl-ester （L-NAME）, blocked the BNP response （in controls）. Interestingly, responses to BNP in CHF patients were reduced to about one third of those seen in healthy controls （increase in flow： 251% in CHF vs. 908% in controls; P 〈 0.001）. In contrast, the vasodilator responses to ACh and to local heating were only somewhat attenuated in CHF patients. Thus, dilator capacity and nitric oxide signalling were not af- fected to the same extent as BNP-mediated dilation, indicating a specific downregulation of the latter response. Conclusions The findings show for the first time that microvascular responses to BNP are markedly reduced in CHF patients. This is consistent with the hypothesis of BNP receptor function is downregulated in CHF.

Atrial natriuretic peptide signal pathway upregulated in stomach of streptozotocin-induced diabetic mice

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.

Plasma brain natriuretic peptide level in older outpatients with heart failure is associated with physical frailty, especially with the slowness domain

Objective To determine the association between plasma brain natriuretic peptide （BNP） level in patients with heart failure （HF） and physical frailty as well as with each domain of physical frailty. Methods Two hundred and six outpatients of cardiovascular medicine aged 60 years and older who had been hospitalized for HF or had been given a prescription medication for HF were included. Physical frailty was assessed using the following five domains： slowness, weakness, exhaustion, low activity, and shrinking, according to the Cardiovascular Health Study. Patients were divided into nonfi-ailty and frailty groups according to frailty scores. Plasma BNP level was measured. The 6-min walk test was performed to measure endurance. Results Plasma BNP was significantly different between the two groups （frailty group： 158.0 i 214.7 pg/mL, nonfrailty group： 65.2 ~ 88.0 pg/mL, P 〈 0.01）. Multivariate logistic regression analysis revealed log-transformed plasma BNP （Log BNP） was significantly associated with physical frailty （OR： 1.68, 95% CI： 1.11-2.56）, and Log BNP was significantly associated with the slowness domain （walking speed 〈 1.0 m/s） of physical frailty （OR： 1.75, 95% Ch 1.15-2.67）. Additionally, Log BNP was negatively correlated to the 6-minute walk distance （6MWD） （p=0.37, P 〈 0.01）, while 6MWD was positively correlated to walking speed （p = 0.66, P 〈 0.01）. Conclusions Plasma BNP level was related to physical frailty, especially in the slowness domain. Endurance may intervene in the associations between plasma BNP level and walking speed.

Effect of atrial natriuretic peptide on ischemia-reperfusion injury in a porcine total hepatic vascular exclusion model

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 flow （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 significantly different between the two groups （60 min： 568.7 ± 113.3 vs 321.6 ± 60.1, P = 0.038 〈 0.05, 120 rain： 673.6± 148.2 vs 281.1±44.8, P = 0.004 〈 0.01）. No significant difference was observed in the TNF-α levels between the two groups. HTBF was higher in the ANP group, but the difference was not significant. A significantly higher level of phosphorylated p38 MAPK was observed in the ANP group compared to the control group （0min： 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.