Background: Hypertension (HTN) is present in up to 90% of end stage kidney disease (ESRD) patients irrespective of the etiology of their kidney disease. Moreover, it is an important modifiable risk factor for progress...Background: Hypertension (HTN) is present in up to 90% of end stage kidney disease (ESRD) patients irrespective of the etiology of their kidney disease. Moreover, it is an important modifiable risk factor for progression to ESRD and its overall cardiovascular morbidity and mortality. Objective: to evaluate, prospectively, the role of Renin-Angiotensin-Aldosterone System blockade (RAAS) in HTN, resistant to 3 conventional antihypertensives, in patients on maintenance hemodialysis (MHD). Patients and methods: A total of 52 such patients were treated with Ramipril and 5 with Losartan after intolerable cough/shortness of breath following Ramipril-use. None of the patients had fluid depletion, renal artery stenosis and primary endocrinopathy. The study group was compared to a matched control group of MHD patients with normal blood pressure following 3 drugs-combination therapies. Results: All patients, with resistant HTN, had significant activation of RAAS system prior to treatment compared to inactive one in the control group. In those with resistant HTN, control of HTN, was established within 2 weeks of therapy and was associated with suppression of the RAAS. Such therapy was associated with minor side effects. Conclusion: Our study has shown that RAAS blockade is safe and effective in controlling such resistant HTN in MHD patients.展开更多
The expression of angiotensin Ⅱ type 1 receptor (AT1R) and angiotensin Ⅱ type 2 receptor (AT2R) in aldosterone-producing adenoma (APA) of the adrenal gland was detected, and their relationship with clinical indexes ...The expression of angiotensin Ⅱ type 1 receptor (AT1R) and angiotensin Ⅱ type 2 receptor (AT2R) in aldosterone-producing adenoma (APA) of the adrenal gland was detected, and their relationship with clinical indexes of APA was analyzed. The mRNA expression of AT1R and AT2R in 50 cases of APA and tissues adjacent to tumors and 12 cases of normal adrenal tissues was detected by using reverse transcriptase polymerase chain reaction (RT-PCR). The expression of AT1R and AT2R proteins in paraffin-embedded slices of tissue was detected by immunohistochemistry. The expression of AT1R in adenoma, tissues adjacent to tumor, and normal tissues of the adrenal gland showed no significant differences. The expression of AT2R in APA tissue was lower than that in normal adrenal gland tissues (P<0.05). Correlation analysis of the mRNA expression level of AT2R and clinical data from patients demonstrated that AT2R expression was negatively related to plasma aldosterone concentration (PAC) (r=-0.467, P<0.05), but positively related with plasma renin activity (PRA) (r=0.604, P<0.05). It is concluded that down-regulation of the AT2R expression is possibly related with the tumorigenesis of APA.展开更多
Previous Background: Hemodynamic factors, like blood pressure, have been established to be major determinants of cardiac left ventricular structure. However, several factors other than blood pressure to influence card...Previous Background: Hemodynamic factors, like blood pressure, have been established to be major determinants of cardiac left ventricular structure. However, several factors other than blood pressure to influence cardiac mass have been implicated. When we did medical survey, cardiac left ventricular mass index (LVMI) of one ethnic group that had higher blood pressure was found to be smaller than that of the other ethnic groups with a lower blood pressure. Such contradicted data from the present study were analyzed combining blood pressure, LVMI and chemical parameters obtained from blood and urine. Methods: In a medical survey conducted in Xinjiang, China, 279 people (65 - 70 years old) from three ethnic groups (Kazakh, Uygur and Han) from two separated regions provided blood and urine samples and underwent echocardiography and 24-h ambulatory blood pressure monitoring (ABPM). Results: Systolic and diastolic blood pressure obtained from ABPM and urinary sodium excretion values were significantly higher in Kazakh than that in Uygur and Han. However, LVMI in Kazakh was lower than that in other 2 groups. Plasma aldosterone concentration (PAC) and plasma renin activity (PRA) were significantly lowest in Kazakh. The values of LVMI in all ethnic groups were positively related to both blood pressure and PAC. An inverse correlation was identified between PAC and urinary sodium excretion value. Conclusion: Although higher blood pressure in Kazakh subjects, their LVMI was lower than those of Uygur and Han, whose blood pressure was lower than that in Kazakh. These results suggest that blood pressure is not always a determinant for LVMI value. There is a possibility that relatively lower PAC resulted from higher sodium intake suppressed the rise in LVMI caused by higher blood pressure in Kazakh.展开更多
Aldosterone quantification helps evaluate the rennin-angiotensin-aldosterone system. The new bead-based mul-tiplex platform has not been applied in aldosterone detection to achieve simultaneous measurements of multipl...Aldosterone quantification helps evaluate the rennin-angiotensin-aldosterone system. The new bead-based mul-tiplex platform has not been applied in aldosterone detection to achieve simultaneous measurements of multiple hormones. A new sensitive competitive bead immunoassay based on Luminex technology for detecting aldoster-one in small sample volumes was developed using two-antibody coupled beads and biotinylated aldosterone as tracer in combination with an extraction step. The assay was validated in human and mouse samples and exhibited a linear working range from 10 to 1,000 pg/mL. The assay was reproducible and precise with intra-assay coeffi-cient of variations (CVs) from 6.0% to 11.2%, inter-assay CVs from 8.0% to 13.0% and good recovery [(90-110)%] and linearity [(89-107)%]. Excellent correlation was found between this new assay and the reference method (r = 0.96, P 0.000,1). The successful establishment of this assay provides high possibility for carrying out bead-based multiplex assay measuring aldosterone and other parameters simultaneously in one 50 μL sample so that the efficiency can be improved and precious samples can be saved.展开更多
The aim of this study was to examine the effects of endoplasmic reticulum (ER) stress on aldosterone (Aldo)-induced apoptosis of endothelial cells. Glucose-regulated protein 78 (GRP78) and C/EBP homologous prote...The aim of this study was to examine the effects of endoplasmic reticulum (ER) stress on aldosterone (Aldo)-induced apoptosis of endothelial cells. Glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP, a hallmark of ER-associated apoptosis) were used to evaluate ER stress. Western blotting and real-time PCR were used to analyze indicators of ER molecule. Apoptosis was detected by annexin V/propidium iodide staining and flow cytometry. Human umbilical vein endo- thelial cells (HUVECs) were stimulated with different concentrations of Aldo for different durations. Aldo promoted apoptosis of HUVECs and induced ER stress, as evidenced by increased expression of GRP78 and CHOP. siRNA knockdown of CHOP attenuated Aldo-mediated apoptosis. These results in- dicate that ER stress may be involved in Aldo-induced apoptosis of HUVECs.展开更多
Quinoxaline 1, 4-dioxides (QdNOs) are quinox-aline derivatives which have been used as an-timicrobial agents and growth promoters in animals widely. They are also assumed to cure human disease such as anticancer, anti...Quinoxaline 1, 4-dioxides (QdNOs) are quinox-aline derivatives which have been used as an-timicrobial agents and growth promoters in animals widely. They are also assumed to cure human disease such as anticancer, antitubercular and inhibiting parasite. QdNOs such as carbadox and their major metabolites induced a special decline of aldosterone production from the swine adrenal in vivo and in vitro, and thus cause hypovolemia, hyponatremia and hyperkalemia. This can also be expected to be the case for human. As a mainly physiological hormone and a novel steroid with potent mineralocorticoid activity, aldosterone plays an important role in the pathophysiological process of brain, renal and heart disease progression and may be a renal and vascular risk factor. Here, we provide evidence to support the hypothesis that QdNOs may lead potential benefits in aldosterone dysmetabolism disease via the synthesis deficiency of aldosterone in adrenal and/or the cardiovascular tissues. If the hypothesis is true, it may provide a new option into the therapy for aldosterone dysmetabolism disease, especially in cardiovascular system, and thus assume a broader application of QdNOs.展开更多
Obstructive sleep apnea(OSA) is an independent risk factor for cardiovascular diseases. Aldosterone was reported to be increased in patients with OSA and correlated with OSA severity. Many studies investigated the e...Obstructive sleep apnea(OSA) is an independent risk factor for cardiovascular diseases. Aldosterone was reported to be increased in patients with OSA and correlated with OSA severity. Many studies investigated the effect of continuous positive airway pressure(CPAP) therapy on plasma aldosterone concentrations(PAC) in OSA patients. The results, however, were inconsistent. In the present study, we aimed to evaluate the effects of CPAP therapy on PAC by performing a meta-analysis. Literature search was carried out in electronic databases including Pub Med/Medline, Cochrane Library, Embase and Web of Science. Eligible full-text articles were identified, and important data were extracted. Pooled analysis was performed using the STATA12.0 and Rev Man 5.2. Standardized mean difference(SMD) was calculated to estimate the treatment effects. A total of eight studies involving 219 patients were included for our final analysis. PAC was found unchanged after CPAP treatment in OSA patients(SMD=-0.36, 95% CI: -0.91 to 0.18, Z=1.32, P=0.19). Meanwhile, CPAP therapy showed no impact on PAC(SMD=-0.21, 95% CI: -0.85 to 0.42, Z=0.66, P=0.51) in a separate meta-analysis including 3 randomized controlled trials. In conclusion, the evidence for the use of CPAP therapy to decrease PAC in OSA patients is low, and further studies are still warranted.展开更多
PK11195, a ligand of peripheral-type benzodiazepine receptor can stimulate thealdosterone secretion of isolated adrenal glomerulosa cell: this effect could be abolished by nifedipinewhich mainly blocks the calcium cha...PK11195, a ligand of peripheral-type benzodiazepine receptor can stimulate thealdosterone secretion of isolated adrenal glomerulosa cell: this effect could be abolished by nifedipinewhich mainly blocks the calcium channel in plasma membrane, but could not be abolished bydantrolene, a selective blocker of mitochondria calcium channel. Even under the condition of themaximum stimulative effects on aldosterone secretion, PK11195 could not change the cyclic AMP(cAMP) content in isolated glomerulosa cells. These results indicated that in the modulatory mecha-nism of benzodiazepine receptor on aldosterone secretion, the intracellular messenger might be theCa<sup>2+</sup> from extracellular Ca<sup>2+</sup> pool, but not the Ca<sup>2+</sup> from mitochondria Ca<sup>2+</sup> pool or cAMP.展开更多
Na+ transport occurs across many epithelial surfaces and plays a key role in regulating salt and water absorption. The molecular pathway underlying this Na+ transport is the epithelial Na channel (ENaC), which is stri...Na+ transport occurs across many epithelial surfaces and plays a key role in regulating salt and water absorption. The molecular pathway underlying this Na+ transport is the epithelial Na channel (ENaC), which is strictly determined by a variety of hormones like aldosterone, ADH and glucocorticoids. In this study, we found that stimulation of either aldosterone or dexameth- asone (Dex) distributed ENaC channel on the apical membrane of mouse cortical collecting duct cells (M1). In the single channel recordings from excised membrane, high density ENaC was found in the cell with a dome shape by the treatment of either dex or aldosterone. However, low active ENaC was revealed in intact cells treated with dex, when compared to cells treated with aldosterone. Only 5.84% of cells treated with dex containing ENaC exhibited ENaC current transition in the cell-attach recording, whereas 40% of cells treated with aldosterone containing ENaC exhibited ENaC current transition. ENaC currents appeared rapid rundown within 5 min-utes since formation of inside-out configuration in cells treated with aldosterone but not with dex. SKF-525A, a general antagonist of CYP, failed to significantly enhance ENaC activity in intact cells treated with dex, but EGTA, which deforming the cells, increased the ENaC activity in the cells treated with dex. PTX, an antagonist of G-protein, reversed the effect of aldosterone on number of active ENaC in intact cells. Based on our obser-vation, we concluded that there are different mechanisms in regulation of ENaC activity be-tween stimulation of aldosterone and glucocor-ticoids. The activation of G-protein is required to maintain the activity of ENaC in the collecting ducts.展开更多
In this article, we describe the clinical picture and follow-up of two children diagnosed as suffering from pseudohypoaldosteronism when they were infants, and it was later recognized as isolated aldosterone deficienc...In this article, we describe the clinical picture and follow-up of two children diagnosed as suffering from pseudohypoaldosteronism when they were infants, and it was later recognized as isolated aldosterone deficiency in both. We illustrate the clinical differences between the two patients in terms of hydroelectrolytic balance, laboratory data and growth. In fact, while the growth and hematological parameters of the electrolytes and acid-base balance were normal in the first patient, and also without treatment with fludrocortisone thanks to very high renin activity, in the second patient, this treatment was vitally necessary to maintain normal growth and biochemical data. Despite the absence of a molecular analysis which could have confirmed this diagnosis, we believe that the description of the clinical evolution of these two cases from the moment of the incorrect diagnosis until the correct diagnosis and action taken, could be useful to highlight the extreme clinical variability of this rare disease.展开更多
Objective:A cell model of cardiac fibroblasts proliferation induced by aldosterone was established to observe the effect of aldosterone on the proliferation of rat cardiac fibroblasts.Methods:Primary cardiac fibroblas...Objective:A cell model of cardiac fibroblasts proliferation induced by aldosterone was established to observe the effect of aldosterone on the proliferation of rat cardiac fibroblasts.Methods:Primary cardiac fibroblasts were cultured by trypsin digestion method and differential adhesion method,primary cardiac fibroblasts were sub-cultured by conventional digestion method,and the immunocytochemical assay was used to identify cardiac fibroblasts.The second-generation cardiac fibroblasts were randomly divided into five groups:standard control group,10-9 mol/L aldosterone(ALD1)group,10-8 mol/L aldosterone(ALD2)group,10-7 mol/L aldosterone(ALD3)group,and 10-6 mol/L aldosterone(ALD4)group.The viability of fibroblast cells in each group was detected by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method.Results:Vimentin staining assay showed that the cultured cells staining positive,and the purity of cultured mouse cardiac fibroblasts was 95%.The results of methyl thiazolyl tetrazolium showed that compared with the control group,the low concentration of aldosterone(10-9 mol/L)had no significant effect on the proliferation of normal cardiac fibroblasts.With the increase in the intensity of(10-8–10-6)mol/L,aldosterone could significantly promote the proliferation of cardiac fibroblasts.Moreover,there was no significant difference in absorbance value between the aldosterone group(10-6 mol/L)and the aldosterone group(10-7 mol/L)(P>0.05).The highest concentration of aldosterone group 10-7 mol/L promoted the proliferation of cardiac the optimum concentration was 10-7 mol/L.Conclusion:Aldosterone can promote the spread of cardiac fibroblasts in a specific concentration range.展开更多
Objective To assess the effect of combined spinal-epidural anesthesia (CSEA) for caesarean section on maternal and neonatal rennin-angiotensin-aldosterone system (RAAS). Methods Sixty ASA I primiparae aged 22-29 yr, w...Objective To assess the effect of combined spinal-epidural anesthesia (CSEA) for caesarean section on maternal and neonatal rennin-angiotensin-aldosterone system (RAAS). Methods Sixty ASA I primiparae aged 22-29 yr, weighing 46 - 83 kg, scheduled for elective caesarean section were randomized into epidural anesthesia group (EA, n = 30) and combined spinal-epidural anesthesia group ( CSEA, n = 30). All patients were premedicated with intramuscular atropine 0. 5 mg and phenolbarbital 100 mg. In CSEA group a 26 G/16 GChina Medical Abstracts (Surgery) single use spinal/epidural needle (B- D) was used. Spinal and/or epidural anesthesia was performed at L2-3 interspace and a catheter was threaded into the epidural space cephalad for 3 - 5 cm in both groups. In EA group a loading dose of 12 - 16 ml 2 % lidocaine was given and an additional 6-8 ml 2% lidocaine was injected when anesthesia became indadequate during the operation. In CSEA group 2.0-2.5 ml hyperbaric 0.5% bupivacaine (10 - 12.5 mg) was given展开更多
Background: Dialysis centres around the world use different concentrations of calcium in dialysate solution,ranging from 1. 25 to 1. 75 mmol / L. However,a dialysate concentration of 1. 25 mmol / L is recommended. [1]...Background: Dialysis centres around the world use different concentrations of calcium in dialysate solution,ranging from 1. 25 to 1. 75 mmol / L. However,a dialysate concentration of 1. 25 mmol / L is recommended. [1] Higher or lower dialysate calcium concentrations are indicated in patients,depending on their co-morbid factors. We explored the effects of using a calcium dialysate solution of 1. 50 mmol / L compared to a 1. 75 mmol / L calcium dialysate solution on the Blood Pressure (BP) ,serum concentrations of Calcium,Parathyroid Hormone (PTH) and Aldosterone in chronic hemodialysis (HD) patients. Method: 42 patients were enrolled in the study. First a 1. 50 mmol / L low calcium dialysate solution (LCDS) was used for 4 hour dialysis,and for the next session of HD,a 1. 75 mmol / L (NCDS) normal calcium dialysate solution was used. Blood pressure was measured at 5 intervals of time: pre HD,at 60,120,180 and 240 minutes into the HD session. Pre and post HD blood samples were taken for serum calcium,PTH and Aldosterone levels. Results: All 42 patients completed the study. With LCDS,the post HD serum calcium levels were (2. 51 ± 0. 14) mmol / L,compared to (2. 85 ± 0. 17) mmol / L for NCDS (P < 0. 01) . A post HD serum PTH level of (80. 6 ± 144. 93) pg / ml was observed when using LCDS,whereas a (52. 25 ± 115. 89) pg / ml serum PTH level was noted with NCDS (P < 0. 01) . As for aldosterone,a post HD value of (161. 77 ± 80. 42) ng / L was obtained with LCDS and (165. 50 ± 78. 84) ng / L with NCDS (P < 0. 01) . The mean post HD systolic blood pressure was (129. 17 ± 25. 42) mmHg with LCDS dialysis compared to (132. 50 ± 20. 32) mmHg for NCDS dialysis (P < 0. 01) and the diastolic BP values observed were (75. 10 ±10. 34) mmHg and (78. 26 ±11. 63) mm Hg(P <0. 01) ,respectively. Conclusion: LCDS can more effectively improve hypercalcemic status in dialysis patients than NCDS. Using LCDS stimulates the secretion of PTH more than when using NCDS. LCDS decreases aldosterone levels more than NCDS. Patients undergoing dialysis with LCDS have a lower post dialysis BP compared to those using NCDS. LCDS has a greater effect in decreasing both the post systolic and diastolic blood pressure than NCDS. Serum calcium,PTH and aldosterone levels have a greater decreasing effect on BP in LCDS than NCDS. Dialysate calcium profiling might be used as a means of therapy to control hypercalcemia, especially in patients who are hemodynamically stable.展开更多
Objective: To determine whether vasculature depends on circulatory or locally produced renin toinitiate its renin angiotensin-aldosterone system (RAAS), and to evaluate the effect of nephrectomy on vascular aldosteron...Objective: To determine whether vasculature depends on circulatory or locally produced renin toinitiate its renin angiotensin-aldosterone system (RAAS), and to evaluate the effect of nephrectomy on vascular aldosterone biosynthesis. Methods: The expression of vascular renin mRNA was observed by reversetranscription polyrnerase chain reaction (RT-PCR) 30 h after nephrectomy, and the production of aldosteroneand angiotensin Ⅱ in vessels measured by high performance liquid chromatography (HPLC) and radioimmunoassay (RIA). Results: Aorta was still able to express renin mRNA after nephrectorny when plasmarenin activity disappeared. There were no significant differences among the control group, the sham operationgroup and the nephrectomy group for both the levels of aldosterone and angiotensin Ⅱ (P >0. 05) althoughthe levels of both ACTH and potassium were significantly increased in the nephrectomy group as comparedwith the control group (P <0. 01 ). However, there were significant differences between the control groupand ACEI-perindopril group for both aldosterone and angiotensin Ⅱ (P <0. 05). Conclusion: The resultssuggest that there exists an independent RAAS in vasculature which is different from that of the heart whichdepends on plasma renin and the biosynthesis of vascular aldosterone is induced mainly by angiotensin Ⅱ.展开更多
BACKGROUND Primary hyperaldosteronism(PH)is considered to contribute to increased risk of developing type 2 diabetes mellitus(T2DM)and prediabetes.Both PH and DM are associated with increased risk for hypertension,car...BACKGROUND Primary hyperaldosteronism(PH)is considered to contribute to increased risk of developing type 2 diabetes mellitus(T2DM)and prediabetes.Both PH and DM are associated with increased risk for hypertension,cardiovascular diseases,and chronic kidney diseases.However,data on prevalence of T2DM and prediabetes in PH,and impact of T2DM and prediabetes on presentation and cardio renal complications in PH at presentation is sparse.AIM To determine the prevalence of T2DM and prediabetes in PH at diagnosis and impact on presentation and complications of PH.METHODS A retrospective cohort study was conducted in tertiary care settings in individuals with confirmed diagnosis of PH at presentation.Demographic variables,clinical presentations,duration and degree of hypertension,complications,laboratory parameters including sodium,potassium levels,plasma aldosterone concentration(PAC),plasma renin activity(PRA),and aldosterone to renin ratio(ARR)and cardio-renal parameters were collected.Comparison was done between three groups:PH with no DM(Group A)or with pre-diabetes(Group B)or with T2DM(Group C).P<0.05 was statistically significant.RESULTS Among 78 individuals with confirmed PH,62%had pre-diabetes or diabetes;with 37%having DM.Mean duration of T2DM was 5.97±4.7 years.The mean levels of glycaemic parameters among the group A vs B vs C individuals were fasting plasma glucose(mg/dL):87.9±6.5,105.4±9.02,130.6±21.1;post prandial plasma glucose(mg/dL):122.7±9.8,154.9±14,196.7±38.0;glycated haemoglobin(%)(5.3±0.2,5.9±0.2,7.5±0.6,P<0.05),respectively.There was no significant difference in the biochemical parameters(PAC,PRA,ARR,sodium,potassium levels),presentation and complications between the groups.Cardio renal parameters or degree and duration of hypertension were comparable between the groups.CONCLUSION Significant prevalence of T2DM and prediabetes in PH at diagnosis does not impact its presentation or complications.Early screening for undetected PH in T2DM and prediabetes subjects with hypertension may prevent complications.展开更多
Emerging evidence indicates that aldosterone and mineralocorticoid receptors (MRs) are associated with the pathogenesis of erectile dysfunction. However, the molecular mechanisms remain largely unknown. In this stud...Emerging evidence indicates that aldosterone and mineralocorticoid receptors (MRs) are associated with the pathogenesis of erectile dysfunction. However, the molecular mechanisms remain largely unknown. In this study, freshly isolated penile corpus cavernosum tissue from rats was treated with aldosterone, with or without MRs inhibitors. Nuclear factor (NF)-kappa B (NF-κB) activity was evaluated by real-time quantitative PCR, luciferase assay, and immunoblot. The results demonstrated that mRNA levels of the NF-κB target genes, including inhibitor of NF-κB alpha (IκB-α, NF-κB1, tumor necrosis factor-alpha (TNF-α, and interleukin 6 (IL-6), were higher after aldosterone treatment. Accordingly, phosphorylation of p65/RelA, IκB-α, and inhibitor of NF-κB kinase-β was markedly increased by aldosterone. Furthermore, knockdown of MRs prevented activation of the NF-κB canonical pathway by aldosterone. Consistent with this finding, ectopic overexpression of MRs enhanced the transcriptional activation of NF-κB by aldosterone. More importantly, the MRs antagonist, spironolactone blocked aldosterone-mediated activation of the canonical NF-κB pathway. In conclusion, aldosterone has an inflammatory effect in the corpus cavernosum penis, inducing NF-κB activation via an MRs-dependent pathway, which may be prevented by selective MRs antagonists. These data reveal the possible role of aldosterone in erectile dysfunction as well as its potential as a novel pharmacologic target for treatment.展开更多
Serum aldosterone is associated with cardiac remodeling,which contributes to morbidity and mortality in heart failure(HF);however,the prognostic value of aldosterone in HF with a preserved ejection fraction(HFpEF)is u...Serum aldosterone is associated with cardiac remodeling,which contributes to morbidity and mortality in heart failure(HF);however,the prognostic value of aldosterone in HF with a preserved ejection fraction(HFpEF)is unclear.We used liquid chromatography-tandem mass spectrometry to quantify serum aldosterone in 873 patients with HFpEF in a Registry Study of Biomarkers for HF.The retrospective study was conducted at Beijing Anzhen Hospital from May 2017 to October 2019.The primary endpoint was a composite of all-cause mortality and rehospitalization for HF.Aldosterone concentrations in patients with and without events were 124.22 pmol L^(-1)(interquartile range(IQR):48.62–256.20)and 96.33 pmol L^(-1)(IQR:37.33–215.76),respectively(P=0.023).Aldosterone independently predicted all-cause mortality(adjusted hazard ratio(aHR),1.55;95%confidence interval(95%CI),1.06–2.27;P=0.024)and the primary endpoint(a HR,1.43;95%CI,1.11–1.85;P=0.006).Patients with high aldosterone concentrations were at higher risk of concentric remodeling(adjusted odds ratio(aOR),1.45;95%CI,1.03–2.04;P=0.034).Patients with high aldosterone and B-type natriuretic peptide concentrations were at a higher risk of the primary endpoint(hazard ratio(HR),1.85;95%CI,1.29–2.66;P=0.001).We conclude that elevated aldosterone is associated with a risk of rehospitalization with HF and all-cause mortality in patients with HFpEF.展开更多
In recent years,Percutaneous coronary intervention(PCI) as an effective treatment for coronary heart disease has been widely carried out in China.However,people is still confronted with the problem that the incidence ...In recent years,Percutaneous coronary intervention(PCI) as an effective treatment for coronary heart disease has been widely carried out in China.However,people is still confronted with the problem that the incidence of in-stent restenosis (ISR) after PCI.Some risk factors of coronary heart disease have been obviously known,but the in-dependent predictor factors for the ISR has not been clear.Clarifying risk factors for ISR to establish interfering meas-ures may be a new direction for PCI treatment in the future.At present,it has been reported that aldosterone (ALD) may be involved in ISR.In order to further investigate the relationship between the serum ALD levels and ISR,our re-search was to determine the ALD and other serum markers to explore the impact factors of ISR.Methods We meas-ured serum ALD,high sensitivity C-reactive protein (hs-CRP) ,adiponectin (ADP) and other indicators in 258 pa-tients with coronary stenting,and made routine follow-up for 6-9 months to perform coronary angiography.According to the results of coronary angiography,all patients were divided into restenosis group and non-restenosis group.We an-alyzed the relationship between ALD,other indicators and ISR to explore whether serum ALD was an independent risk factor ISR.Results Serum ALD levels were significantly higher in restenosis group than non-restenosis group.Logis-tic regression analysis showed that diabetes,ALD,hs-CRP and complex lesions were also independent risk factors for ISR (P < 0.05) ,while the ADP was as a protective factor for ISR (P < 0.05) .Conclusions ALD is one of inde-pendent risk factors for ISR after undergoing coronary stent implantation in patients.It has the possibility of becoming one new method in this medical field.展开更多
The determination of the plasma level of aldosterone is very helpful to the diagnosis of aldosteronism. A radioimmunoassay for plasma aldosterene was first established in the Department of Endocrinology of the Capital...The determination of the plasma level of aldosterone is very helpful to the diagnosis of aldosteronism. A radioimmunoassay for plasma aldosterene was first established in the Department of Endocrinology of the Capital Hospital, Beijing in July 1977. Our method and its clinical application are summarized as follows. (1) Preparation of the aldosterone-3-carboxymethoxime. 9.4mg of aldosterone dissolved展开更多
Background:Since the diagnostic value of aldosterone to renin ratio(ARR)calculated by plasma renin concentration(PRC)or plasma renin activity(PRA)is still inconclusive,we conducted a meta-analysis by systematically re...Background:Since the diagnostic value of aldosterone to renin ratio(ARR)calculated by plasma renin concentration(PRC)or plasma renin activity(PRA)is still inconclusive,we conducted a meta-analysis by systematically reviewing relevant literature to explore the difference in the diagnostic efficacy of ARR calculated by PRC or PRA,so as to provide guidance for clinical diagnosis.Methods:We searched PubMed,Embase,and Cochrane Library from the establishment of the database to March 2021.We included studies that report the true positive,false positive,true negative,and false negative values for the diagnosis of primary aldosteronism,and we excluded duplicate publications,research without full text,incomplete information,or inability to conduct data extraction,animal experiments,reviews,and systematic reviews.STATA 15.1 was used to analyze the data.Results:The pooled results showed that ARR(plasma aldosterone concentration[PAC]/PRC)had a sensitivity of 0.82(95%confidence interval[CI]:0.78-0.86),a specificity of 0.94(95%CI:0.92-0.95),a positive-likelihood ratio(LR)of 12.77(95%CI:7.04-23.73),a negative LR of 0.11(95%CI:0.07-0.17),and symmetric area under the curve(SAUC)of 0.982,respectively.Furthermore,the diagnostic odds ratio(DOR)of ARR(PAC/PRC)was 180.21.Additionally,the pooled results showed that ARR(PAC/PRA)had a sensitivity of 0.91(95%CI:0.86-0.95),a specificity of 0.91(95%CI:0.90-0.93),a positive LR of 7.30(95%CI:2.99-17.99),a negative LR of 0.10(95%CI:0.04-0.26),and SAUC of 0.976,respectively.The DOR of ARR(PAC/PRA)was 155.52.Additionally,we conducted a subgroup analysis for the different thresholds(<35 or≥35)of PAC/PRC.The results showed that the DOR of the cut-off≥35 groups was higher than the cut-off<35 groups(DOR=340.15,95%CI:38.32-3019.66;DOR=116.40,95%CI=23.28-581.92).Conclusions:The research results suggest that the determination of ARR(PAC/PRC)and ARR(PAC/PRA)was all effective screening tools for PA.The diagnostic accuracy and diagnostic value of ARR(PAC/PRC)are higher than ARR(PAC/PRA).In addition,within a certain range,the higher the threshold,the better the diagnostic value.展开更多
文摘Background: Hypertension (HTN) is present in up to 90% of end stage kidney disease (ESRD) patients irrespective of the etiology of their kidney disease. Moreover, it is an important modifiable risk factor for progression to ESRD and its overall cardiovascular morbidity and mortality. Objective: to evaluate, prospectively, the role of Renin-Angiotensin-Aldosterone System blockade (RAAS) in HTN, resistant to 3 conventional antihypertensives, in patients on maintenance hemodialysis (MHD). Patients and methods: A total of 52 such patients were treated with Ramipril and 5 with Losartan after intolerable cough/shortness of breath following Ramipril-use. None of the patients had fluid depletion, renal artery stenosis and primary endocrinopathy. The study group was compared to a matched control group of MHD patients with normal blood pressure following 3 drugs-combination therapies. Results: All patients, with resistant HTN, had significant activation of RAAS system prior to treatment compared to inactive one in the control group. In those with resistant HTN, control of HTN, was established within 2 weeks of therapy and was associated with suppression of the RAAS. Such therapy was associated with minor side effects. Conclusion: Our study has shown that RAAS blockade is safe and effective in controlling such resistant HTN in MHD patients.
基金supported by the National Natural Science Founds for Distinguished Young Scholar of China (No. 30725040)
文摘The expression of angiotensin Ⅱ type 1 receptor (AT1R) and angiotensin Ⅱ type 2 receptor (AT2R) in aldosterone-producing adenoma (APA) of the adrenal gland was detected, and their relationship with clinical indexes of APA was analyzed. The mRNA expression of AT1R and AT2R in 50 cases of APA and tissues adjacent to tumors and 12 cases of normal adrenal tissues was detected by using reverse transcriptase polymerase chain reaction (RT-PCR). The expression of AT1R and AT2R proteins in paraffin-embedded slices of tissue was detected by immunohistochemistry. The expression of AT1R in adenoma, tissues adjacent to tumor, and normal tissues of the adrenal gland showed no significant differences. The expression of AT2R in APA tissue was lower than that in normal adrenal gland tissues (P<0.05). Correlation analysis of the mRNA expression level of AT2R and clinical data from patients demonstrated that AT2R expression was negatively related to plasma aldosterone concentration (PAC) (r=-0.467, P<0.05), but positively related with plasma renin activity (PRA) (r=0.604, P<0.05). It is concluded that down-regulation of the AT2R expression is possibly related with the tumorigenesis of APA.
文摘Previous Background: Hemodynamic factors, like blood pressure, have been established to be major determinants of cardiac left ventricular structure. However, several factors other than blood pressure to influence cardiac mass have been implicated. When we did medical survey, cardiac left ventricular mass index (LVMI) of one ethnic group that had higher blood pressure was found to be smaller than that of the other ethnic groups with a lower blood pressure. Such contradicted data from the present study were analyzed combining blood pressure, LVMI and chemical parameters obtained from blood and urine. Methods: In a medical survey conducted in Xinjiang, China, 279 people (65 - 70 years old) from three ethnic groups (Kazakh, Uygur and Han) from two separated regions provided blood and urine samples and underwent echocardiography and 24-h ambulatory blood pressure monitoring (ABPM). Results: Systolic and diastolic blood pressure obtained from ABPM and urinary sodium excretion values were significantly higher in Kazakh than that in Uygur and Han. However, LVMI in Kazakh was lower than that in other 2 groups. Plasma aldosterone concentration (PAC) and plasma renin activity (PRA) were significantly lowest in Kazakh. The values of LVMI in all ethnic groups were positively related to both blood pressure and PAC. An inverse correlation was identified between PAC and urinary sodium excretion value. Conclusion: Although higher blood pressure in Kazakh subjects, their LVMI was lower than those of Uygur and Han, whose blood pressure was lower than that in Kazakh. These results suggest that blood pressure is not always a determinant for LVMI value. There is a possibility that relatively lower PAC resulted from higher sodium intake suppressed the rise in LVMI caused by higher blood pressure in Kazakh.
文摘Aldosterone quantification helps evaluate the rennin-angiotensin-aldosterone system. The new bead-based mul-tiplex platform has not been applied in aldosterone detection to achieve simultaneous measurements of multiple hormones. A new sensitive competitive bead immunoassay based on Luminex technology for detecting aldoster-one in small sample volumes was developed using two-antibody coupled beads and biotinylated aldosterone as tracer in combination with an extraction step. The assay was validated in human and mouse samples and exhibited a linear working range from 10 to 1,000 pg/mL. The assay was reproducible and precise with intra-assay coeffi-cient of variations (CVs) from 6.0% to 11.2%, inter-assay CVs from 8.0% to 13.0% and good recovery [(90-110)%] and linearity [(89-107)%]. Excellent correlation was found between this new assay and the reference method (r = 0.96, P 0.000,1). The successful establishment of this assay provides high possibility for carrying out bead-based multiplex assay measuring aldosterone and other parameters simultaneously in one 50 μL sample so that the efficiency can be improved and precious samples can be saved.
文摘The aim of this study was to examine the effects of endoplasmic reticulum (ER) stress on aldosterone (Aldo)-induced apoptosis of endothelial cells. Glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP, a hallmark of ER-associated apoptosis) were used to evaluate ER stress. Western blotting and real-time PCR were used to analyze indicators of ER molecule. Apoptosis was detected by annexin V/propidium iodide staining and flow cytometry. Human umbilical vein endo- thelial cells (HUVECs) were stimulated with different concentrations of Aldo for different durations. Aldo promoted apoptosis of HUVECs and induced ER stress, as evidenced by increased expression of GRP78 and CHOP. siRNA knockdown of CHOP attenuated Aldo-mediated apoptosis. These results in- dicate that ER stress may be involved in Aldo-induced apoptosis of HUVECs.
文摘Quinoxaline 1, 4-dioxides (QdNOs) are quinox-aline derivatives which have been used as an-timicrobial agents and growth promoters in animals widely. They are also assumed to cure human disease such as anticancer, antitubercular and inhibiting parasite. QdNOs such as carbadox and their major metabolites induced a special decline of aldosterone production from the swine adrenal in vivo and in vitro, and thus cause hypovolemia, hyponatremia and hyperkalemia. This can also be expected to be the case for human. As a mainly physiological hormone and a novel steroid with potent mineralocorticoid activity, aldosterone plays an important role in the pathophysiological process of brain, renal and heart disease progression and may be a renal and vascular risk factor. Here, we provide evidence to support the hypothesis that QdNOs may lead potential benefits in aldosterone dysmetabolism disease via the synthesis deficiency of aldosterone in adrenal and/or the cardiovascular tissues. If the hypothesis is true, it may provide a new option into the therapy for aldosterone dysmetabolism disease, especially in cardiovascular system, and thus assume a broader application of QdNOs.
文摘Obstructive sleep apnea(OSA) is an independent risk factor for cardiovascular diseases. Aldosterone was reported to be increased in patients with OSA and correlated with OSA severity. Many studies investigated the effect of continuous positive airway pressure(CPAP) therapy on plasma aldosterone concentrations(PAC) in OSA patients. The results, however, were inconsistent. In the present study, we aimed to evaluate the effects of CPAP therapy on PAC by performing a meta-analysis. Literature search was carried out in electronic databases including Pub Med/Medline, Cochrane Library, Embase and Web of Science. Eligible full-text articles were identified, and important data were extracted. Pooled analysis was performed using the STATA12.0 and Rev Man 5.2. Standardized mean difference(SMD) was calculated to estimate the treatment effects. A total of eight studies involving 219 patients were included for our final analysis. PAC was found unchanged after CPAP treatment in OSA patients(SMD=-0.36, 95% CI: -0.91 to 0.18, Z=1.32, P=0.19). Meanwhile, CPAP therapy showed no impact on PAC(SMD=-0.21, 95% CI: -0.85 to 0.42, Z=0.66, P=0.51) in a separate meta-analysis including 3 randomized controlled trials. In conclusion, the evidence for the use of CPAP therapy to decrease PAC in OSA patients is low, and further studies are still warranted.
文摘PK11195, a ligand of peripheral-type benzodiazepine receptor can stimulate thealdosterone secretion of isolated adrenal glomerulosa cell: this effect could be abolished by nifedipinewhich mainly blocks the calcium channel in plasma membrane, but could not be abolished bydantrolene, a selective blocker of mitochondria calcium channel. Even under the condition of themaximum stimulative effects on aldosterone secretion, PK11195 could not change the cyclic AMP(cAMP) content in isolated glomerulosa cells. These results indicated that in the modulatory mecha-nism of benzodiazepine receptor on aldosterone secretion, the intracellular messenger might be theCa<sup>2+</sup> from extracellular Ca<sup>2+</sup> pool, but not the Ca<sup>2+</sup> from mitochondria Ca<sup>2+</sup> pool or cAMP.
文摘Na+ transport occurs across many epithelial surfaces and plays a key role in regulating salt and water absorption. The molecular pathway underlying this Na+ transport is the epithelial Na channel (ENaC), which is strictly determined by a variety of hormones like aldosterone, ADH and glucocorticoids. In this study, we found that stimulation of either aldosterone or dexameth- asone (Dex) distributed ENaC channel on the apical membrane of mouse cortical collecting duct cells (M1). In the single channel recordings from excised membrane, high density ENaC was found in the cell with a dome shape by the treatment of either dex or aldosterone. However, low active ENaC was revealed in intact cells treated with dex, when compared to cells treated with aldosterone. Only 5.84% of cells treated with dex containing ENaC exhibited ENaC current transition in the cell-attach recording, whereas 40% of cells treated with aldosterone containing ENaC exhibited ENaC current transition. ENaC currents appeared rapid rundown within 5 min-utes since formation of inside-out configuration in cells treated with aldosterone but not with dex. SKF-525A, a general antagonist of CYP, failed to significantly enhance ENaC activity in intact cells treated with dex, but EGTA, which deforming the cells, increased the ENaC activity in the cells treated with dex. PTX, an antagonist of G-protein, reversed the effect of aldosterone on number of active ENaC in intact cells. Based on our obser-vation, we concluded that there are different mechanisms in regulation of ENaC activity be-tween stimulation of aldosterone and glucocor-ticoids. The activation of G-protein is required to maintain the activity of ENaC in the collecting ducts.
文摘In this article, we describe the clinical picture and follow-up of two children diagnosed as suffering from pseudohypoaldosteronism when they were infants, and it was later recognized as isolated aldosterone deficiency in both. We illustrate the clinical differences between the two patients in terms of hydroelectrolytic balance, laboratory data and growth. In fact, while the growth and hematological parameters of the electrolytes and acid-base balance were normal in the first patient, and also without treatment with fludrocortisone thanks to very high renin activity, in the second patient, this treatment was vitally necessary to maintain normal growth and biochemical data. Despite the absence of a molecular analysis which could have confirmed this diagnosis, we believe that the description of the clinical evolution of these two cases from the moment of the incorrect diagnosis until the correct diagnosis and action taken, could be useful to highlight the extreme clinical variability of this rare disease.
基金This study was supported by the project of Hebei Provincial Administration of traditional Chinese Medicine(No.2018161)the Hebei Health and Family Planning Commission(No.20170875)the Scientific Research Project of College students in Chengde Medical College(No.2019033).
文摘Objective:A cell model of cardiac fibroblasts proliferation induced by aldosterone was established to observe the effect of aldosterone on the proliferation of rat cardiac fibroblasts.Methods:Primary cardiac fibroblasts were cultured by trypsin digestion method and differential adhesion method,primary cardiac fibroblasts were sub-cultured by conventional digestion method,and the immunocytochemical assay was used to identify cardiac fibroblasts.The second-generation cardiac fibroblasts were randomly divided into five groups:standard control group,10-9 mol/L aldosterone(ALD1)group,10-8 mol/L aldosterone(ALD2)group,10-7 mol/L aldosterone(ALD3)group,and 10-6 mol/L aldosterone(ALD4)group.The viability of fibroblast cells in each group was detected by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method.Results:Vimentin staining assay showed that the cultured cells staining positive,and the purity of cultured mouse cardiac fibroblasts was 95%.The results of methyl thiazolyl tetrazolium showed that compared with the control group,the low concentration of aldosterone(10-9 mol/L)had no significant effect on the proliferation of normal cardiac fibroblasts.With the increase in the intensity of(10-8–10-6)mol/L,aldosterone could significantly promote the proliferation of cardiac fibroblasts.Moreover,there was no significant difference in absorbance value between the aldosterone group(10-6 mol/L)and the aldosterone group(10-7 mol/L)(P>0.05).The highest concentration of aldosterone group 10-7 mol/L promoted the proliferation of cardiac the optimum concentration was 10-7 mol/L.Conclusion:Aldosterone can promote the spread of cardiac fibroblasts in a specific concentration range.
文摘Objective To assess the effect of combined spinal-epidural anesthesia (CSEA) for caesarean section on maternal and neonatal rennin-angiotensin-aldosterone system (RAAS). Methods Sixty ASA I primiparae aged 22-29 yr, weighing 46 - 83 kg, scheduled for elective caesarean section were randomized into epidural anesthesia group (EA, n = 30) and combined spinal-epidural anesthesia group ( CSEA, n = 30). All patients were premedicated with intramuscular atropine 0. 5 mg and phenolbarbital 100 mg. In CSEA group a 26 G/16 GChina Medical Abstracts (Surgery) single use spinal/epidural needle (B- D) was used. Spinal and/or epidural anesthesia was performed at L2-3 interspace and a catheter was threaded into the epidural space cephalad for 3 - 5 cm in both groups. In EA group a loading dose of 12 - 16 ml 2 % lidocaine was given and an additional 6-8 ml 2% lidocaine was injected when anesthesia became indadequate during the operation. In CSEA group 2.0-2.5 ml hyperbaric 0.5% bupivacaine (10 - 12.5 mg) was given
文摘Background: Dialysis centres around the world use different concentrations of calcium in dialysate solution,ranging from 1. 25 to 1. 75 mmol / L. However,a dialysate concentration of 1. 25 mmol / L is recommended. [1] Higher or lower dialysate calcium concentrations are indicated in patients,depending on their co-morbid factors. We explored the effects of using a calcium dialysate solution of 1. 50 mmol / L compared to a 1. 75 mmol / L calcium dialysate solution on the Blood Pressure (BP) ,serum concentrations of Calcium,Parathyroid Hormone (PTH) and Aldosterone in chronic hemodialysis (HD) patients. Method: 42 patients were enrolled in the study. First a 1. 50 mmol / L low calcium dialysate solution (LCDS) was used for 4 hour dialysis,and for the next session of HD,a 1. 75 mmol / L (NCDS) normal calcium dialysate solution was used. Blood pressure was measured at 5 intervals of time: pre HD,at 60,120,180 and 240 minutes into the HD session. Pre and post HD blood samples were taken for serum calcium,PTH and Aldosterone levels. Results: All 42 patients completed the study. With LCDS,the post HD serum calcium levels were (2. 51 ± 0. 14) mmol / L,compared to (2. 85 ± 0. 17) mmol / L for NCDS (P < 0. 01) . A post HD serum PTH level of (80. 6 ± 144. 93) pg / ml was observed when using LCDS,whereas a (52. 25 ± 115. 89) pg / ml serum PTH level was noted with NCDS (P < 0. 01) . As for aldosterone,a post HD value of (161. 77 ± 80. 42) ng / L was obtained with LCDS and (165. 50 ± 78. 84) ng / L with NCDS (P < 0. 01) . The mean post HD systolic blood pressure was (129. 17 ± 25. 42) mmHg with LCDS dialysis compared to (132. 50 ± 20. 32) mmHg for NCDS dialysis (P < 0. 01) and the diastolic BP values observed were (75. 10 ±10. 34) mmHg and (78. 26 ±11. 63) mm Hg(P <0. 01) ,respectively. Conclusion: LCDS can more effectively improve hypercalcemic status in dialysis patients than NCDS. Using LCDS stimulates the secretion of PTH more than when using NCDS. LCDS decreases aldosterone levels more than NCDS. Patients undergoing dialysis with LCDS have a lower post dialysis BP compared to those using NCDS. LCDS has a greater effect in decreasing both the post systolic and diastolic blood pressure than NCDS. Serum calcium,PTH and aldosterone levels have a greater decreasing effect on BP in LCDS than NCDS. Dialysate calcium profiling might be used as a means of therapy to control hypercalcemia, especially in patients who are hemodynamically stable.
文摘Objective: To determine whether vasculature depends on circulatory or locally produced renin toinitiate its renin angiotensin-aldosterone system (RAAS), and to evaluate the effect of nephrectomy on vascular aldosterone biosynthesis. Methods: The expression of vascular renin mRNA was observed by reversetranscription polyrnerase chain reaction (RT-PCR) 30 h after nephrectomy, and the production of aldosteroneand angiotensin Ⅱ in vessels measured by high performance liquid chromatography (HPLC) and radioimmunoassay (RIA). Results: Aorta was still able to express renin mRNA after nephrectorny when plasmarenin activity disappeared. There were no significant differences among the control group, the sham operationgroup and the nephrectomy group for both the levels of aldosterone and angiotensin Ⅱ (P >0. 05) althoughthe levels of both ACTH and potassium were significantly increased in the nephrectomy group as comparedwith the control group (P <0. 01 ). However, there were significant differences between the control groupand ACEI-perindopril group for both aldosterone and angiotensin Ⅱ (P <0. 05). Conclusion: The resultssuggest that there exists an independent RAAS in vasculature which is different from that of the heart whichdepends on plasma renin and the biosynthesis of vascular aldosterone is induced mainly by angiotensin Ⅱ.
文摘BACKGROUND Primary hyperaldosteronism(PH)is considered to contribute to increased risk of developing type 2 diabetes mellitus(T2DM)and prediabetes.Both PH and DM are associated with increased risk for hypertension,cardiovascular diseases,and chronic kidney diseases.However,data on prevalence of T2DM and prediabetes in PH,and impact of T2DM and prediabetes on presentation and cardio renal complications in PH at presentation is sparse.AIM To determine the prevalence of T2DM and prediabetes in PH at diagnosis and impact on presentation and complications of PH.METHODS A retrospective cohort study was conducted in tertiary care settings in individuals with confirmed diagnosis of PH at presentation.Demographic variables,clinical presentations,duration and degree of hypertension,complications,laboratory parameters including sodium,potassium levels,plasma aldosterone concentration(PAC),plasma renin activity(PRA),and aldosterone to renin ratio(ARR)and cardio-renal parameters were collected.Comparison was done between three groups:PH with no DM(Group A)or with pre-diabetes(Group B)or with T2DM(Group C).P<0.05 was statistically significant.RESULTS Among 78 individuals with confirmed PH,62%had pre-diabetes or diabetes;with 37%having DM.Mean duration of T2DM was 5.97±4.7 years.The mean levels of glycaemic parameters among the group A vs B vs C individuals were fasting plasma glucose(mg/dL):87.9±6.5,105.4±9.02,130.6±21.1;post prandial plasma glucose(mg/dL):122.7±9.8,154.9±14,196.7±38.0;glycated haemoglobin(%)(5.3±0.2,5.9±0.2,7.5±0.6,P<0.05),respectively.There was no significant difference in the biochemical parameters(PAC,PRA,ARR,sodium,potassium levels),presentation and complications between the groups.Cardio renal parameters or degree and duration of hypertension were comparable between the groups.CONCLUSION Significant prevalence of T2DM and prediabetes in PH at diagnosis does not impact its presentation or complications.Early screening for undetected PH in T2DM and prediabetes subjects with hypertension may prevent complications.
基金This work was supported by the National Basic Researcla Program or China (2015CB943003) and the National Natural Science Foundation of China (81370753). Dr. Fei Wu received financial support from the China Scholarship Council (CSC 201506100054). We thank Dr. Yang Sun (Department of Dermatology, Qilu Hospital, Shandong University, China) for proofreading of our manuscript and all her supports.
文摘Emerging evidence indicates that aldosterone and mineralocorticoid receptors (MRs) are associated with the pathogenesis of erectile dysfunction. However, the molecular mechanisms remain largely unknown. In this study, freshly isolated penile corpus cavernosum tissue from rats was treated with aldosterone, with or without MRs inhibitors. Nuclear factor (NF)-kappa B (NF-κB) activity was evaluated by real-time quantitative PCR, luciferase assay, and immunoblot. The results demonstrated that mRNA levels of the NF-κB target genes, including inhibitor of NF-κB alpha (IκB-α, NF-κB1, tumor necrosis factor-alpha (TNF-α, and interleukin 6 (IL-6), were higher after aldosterone treatment. Accordingly, phosphorylation of p65/RelA, IκB-α, and inhibitor of NF-κB kinase-β was markedly increased by aldosterone. Furthermore, knockdown of MRs prevented activation of the NF-κB canonical pathway by aldosterone. Consistent with this finding, ectopic overexpression of MRs enhanced the transcriptional activation of NF-κB by aldosterone. More importantly, the MRs antagonist, spironolactone blocked aldosterone-mediated activation of the canonical NF-κB pathway. In conclusion, aldosterone has an inflammatory effect in the corpus cavernosum penis, inducing NF-κB activation via an MRs-dependent pathway, which may be prevented by selective MRs antagonists. These data reveal the possible role of aldosterone in erectile dysfunction as well as its potential as a novel pharmacologic target for treatment.
基金supported by the National Key Research and Development Program of China(2017YFC0908400)the National Natural Science Foundation of China(91939303,81790622,81861128025)。
文摘Serum aldosterone is associated with cardiac remodeling,which contributes to morbidity and mortality in heart failure(HF);however,the prognostic value of aldosterone in HF with a preserved ejection fraction(HFpEF)is unclear.We used liquid chromatography-tandem mass spectrometry to quantify serum aldosterone in 873 patients with HFpEF in a Registry Study of Biomarkers for HF.The retrospective study was conducted at Beijing Anzhen Hospital from May 2017 to October 2019.The primary endpoint was a composite of all-cause mortality and rehospitalization for HF.Aldosterone concentrations in patients with and without events were 124.22 pmol L^(-1)(interquartile range(IQR):48.62–256.20)and 96.33 pmol L^(-1)(IQR:37.33–215.76),respectively(P=0.023).Aldosterone independently predicted all-cause mortality(adjusted hazard ratio(aHR),1.55;95%confidence interval(95%CI),1.06–2.27;P=0.024)and the primary endpoint(a HR,1.43;95%CI,1.11–1.85;P=0.006).Patients with high aldosterone concentrations were at higher risk of concentric remodeling(adjusted odds ratio(aOR),1.45;95%CI,1.03–2.04;P=0.034).Patients with high aldosterone and B-type natriuretic peptide concentrations were at a higher risk of the primary endpoint(hazard ratio(HR),1.85;95%CI,1.29–2.66;P=0.001).We conclude that elevated aldosterone is associated with a risk of rehospitalization with HF and all-cause mortality in patients with HFpEF.
文摘In recent years,Percutaneous coronary intervention(PCI) as an effective treatment for coronary heart disease has been widely carried out in China.However,people is still confronted with the problem that the incidence of in-stent restenosis (ISR) after PCI.Some risk factors of coronary heart disease have been obviously known,but the in-dependent predictor factors for the ISR has not been clear.Clarifying risk factors for ISR to establish interfering meas-ures may be a new direction for PCI treatment in the future.At present,it has been reported that aldosterone (ALD) may be involved in ISR.In order to further investigate the relationship between the serum ALD levels and ISR,our re-search was to determine the ALD and other serum markers to explore the impact factors of ISR.Methods We meas-ured serum ALD,high sensitivity C-reactive protein (hs-CRP) ,adiponectin (ADP) and other indicators in 258 pa-tients with coronary stenting,and made routine follow-up for 6-9 months to perform coronary angiography.According to the results of coronary angiography,all patients were divided into restenosis group and non-restenosis group.We an-alyzed the relationship between ALD,other indicators and ISR to explore whether serum ALD was an independent risk factor ISR.Results Serum ALD levels were significantly higher in restenosis group than non-restenosis group.Logis-tic regression analysis showed that diabetes,ALD,hs-CRP and complex lesions were also independent risk factors for ISR (P < 0.05) ,while the ADP was as a protective factor for ISR (P < 0.05) .Conclusions ALD is one of inde-pendent risk factors for ISR after undergoing coronary stent implantation in patients.It has the possibility of becoming one new method in this medical field.
文摘The determination of the plasma level of aldosterone is very helpful to the diagnosis of aldosteronism. A radioimmunoassay for plasma aldosterene was first established in the Department of Endocrinology of the Capital Hospital, Beijing in July 1977. Our method and its clinical application are summarized as follows. (1) Preparation of the aldosterone-3-carboxymethoxime. 9.4mg of aldosterone dissolved
基金supported by a grant from the Science and Technology Project of Guangdong Province(No.2016A020215136)。
文摘Background:Since the diagnostic value of aldosterone to renin ratio(ARR)calculated by plasma renin concentration(PRC)or plasma renin activity(PRA)is still inconclusive,we conducted a meta-analysis by systematically reviewing relevant literature to explore the difference in the diagnostic efficacy of ARR calculated by PRC or PRA,so as to provide guidance for clinical diagnosis.Methods:We searched PubMed,Embase,and Cochrane Library from the establishment of the database to March 2021.We included studies that report the true positive,false positive,true negative,and false negative values for the diagnosis of primary aldosteronism,and we excluded duplicate publications,research without full text,incomplete information,or inability to conduct data extraction,animal experiments,reviews,and systematic reviews.STATA 15.1 was used to analyze the data.Results:The pooled results showed that ARR(plasma aldosterone concentration[PAC]/PRC)had a sensitivity of 0.82(95%confidence interval[CI]:0.78-0.86),a specificity of 0.94(95%CI:0.92-0.95),a positive-likelihood ratio(LR)of 12.77(95%CI:7.04-23.73),a negative LR of 0.11(95%CI:0.07-0.17),and symmetric area under the curve(SAUC)of 0.982,respectively.Furthermore,the diagnostic odds ratio(DOR)of ARR(PAC/PRC)was 180.21.Additionally,the pooled results showed that ARR(PAC/PRA)had a sensitivity of 0.91(95%CI:0.86-0.95),a specificity of 0.91(95%CI:0.90-0.93),a positive LR of 7.30(95%CI:2.99-17.99),a negative LR of 0.10(95%CI:0.04-0.26),and SAUC of 0.976,respectively.The DOR of ARR(PAC/PRA)was 155.52.Additionally,we conducted a subgroup analysis for the different thresholds(<35 or≥35)of PAC/PRC.The results showed that the DOR of the cut-off≥35 groups was higher than the cut-off<35 groups(DOR=340.15,95%CI:38.32-3019.66;DOR=116.40,95%CI=23.28-581.92).Conclusions:The research results suggest that the determination of ARR(PAC/PRC)and ARR(PAC/PRA)was all effective screening tools for PA.The diagnostic accuracy and diagnostic value of ARR(PAC/PRC)are higher than ARR(PAC/PRA).In addition,within a certain range,the higher the threshold,the better the diagnostic value.