The Beneficial Effect of Renin-Angiotensin-Aldosterone System Blockade in Treatment of Hypertension, Resistant to Conventional Antihypertensives, in Patients on Maintenance Hemodialysis

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.

Prevalence and impact of diabetes and prediabetes on presentation and complications of primary hyperaldosteronism at diagnosis

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.

Effects of highly potent atrial natriuretic peptide on circulating reninangiotensin-aldosterone system and cardiac function in dogs with ischemic heart failure

The effects of highly-potent atrial natriuretic peptide (HPANP) on circulating re nin-angiotensin-aldos-terone system (RAAS) and cardiac function were studied in an acute ischemic heart failure model. HPANP (6 μg/kg and 3 μg/kg) was infused intracoronarily. It was found that both doses of HPANP could cause significant decrease in plasma renin activity (PRA), angiotensin II (AII) and aldosterone (Ald). After the administraticn of HPANP, PRA, AII and Ald in the coronary sinus were decreased by 73. 2% (P<0.01), 68. o% (P<0.01) and 73. 6% (P<0.01), and the hormones in peripheral venous blood by 63. 3% (P<0.01), 53. 3% (P<0.01) and 64. 9% (P<0.01), respectively at the dose of 6 μg/kg. While PRA, AII and Ald in the coronary sinus and in peripheral venous blood decreased by 55. 9%, 55. 3%, 61. 9%, and 54. 0%, 42. 3%, 53, 3%, respectively at the 3μg/kg dose level. At the higher dose, HPANP increased left ventricular systolic pressure (LVSP, +13. 1%, P<0. 05), +dP/dtmax(+24.1 %, P<0.01), -dp/dtmax (+35.9%, P<0.01), and VCE(+28.9%, P<0.05). Mean arterial pressure and left ventricular end-diastolic pressure (LVEDP) were decreased (-15.0%, P<0.01, and 29. 6%, P<0.01, respectively). In contrast, the lower dose caused no significant changes of LVSP, +dp/dtmex,dp/dtmax and VCE(not including LVEDP, - 20. 5 %, P<0.05). Neither of the doses caused significant changes in heart rate and T value- Normal saline infusion has no effects on cardiac function and circulating RAAS- We conclude that in ischemic heart failure, intracoronary administration of HPANP can significantly suppress the activity of circulating RAAS, and improve cardiac function by reducing pre- and after-load of the heart, but has no direct myocardial effects.

Association between renin-angiotensin system inhibitor and the risk of CMV pneumonia:a Mendelian randomization study

Background:Cytomegalovirus(CMV)reactivation is linked to a high mortality rate,especially among the elderly.Prior research suggests that renin-angiotensin system(RAS)inhibitors may influence both the onset and prognosis of pneumonia.This study aims to examine the causal relationship between RAS inhibitor use and the risk of CMV pneumonia using Mendelian randomization(MR)analysis.Methods:We conducted an analysis using data from two genome-wide association studies(GWAS)involving individuals of European ancestry.This dataset included individuals treated with RAS inhibitors and those with CMV pneumonia.We assessed the relationship between RAS inhibitor use and CMV pneumonia risk using the inverse variance weighted(IVW)method.The results were further evaluated for pleiotropy,heterogeneity,and robustness.Results:The Mendelian randomization(MR)analysis revealed a causal relationship between RAS inhibitor use and an increased risk of CMV pneumonia(IVW:odds ratio[OR]=2.73;95%confidence interval[CI]=1.11-6.73;P=0.028).Conclusions:Our finding indicate a positive causal relationship between the use of RAS inhibitors and the onset of CMV pneumonia.

龙蛇九味汤联合坎地沙坦酯片对高血压患者Renin、AngⅡ与ALD的影响

目的:研究龙蛇九味汤联合坎地沙坦酯片治疗高血压的疗效及其对患者肾素(Renin)、血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)及醛固酮(aldosterone,ALD)水平的影响。方法:将高血压患者99例按照随机数字表法分为观察组(50例,予龙蛇九味汤联合坎地沙坦酯片治疗)和对照组(49例,予坎地沙坦酯片治疗)。比较两组治疗效果,观察两组患者治疗前后甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)及低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)水平。检测两组患者治疗前后血浆Renin、AngⅡ及ALD水平。结果:观察组疗效优于对照组(P<0.05);治疗后观察组TG、TC、LDL-C及血压晨峰值、收缩压、舒张压以及血浆Renin、AngⅡ、ALD均低于对照组(P<0.05),HDL-C高于对照组(P<0.05)。结论:龙蛇九味汤联合坎地沙坦酯有助于纠正高血压患者血脂紊乱情况,提高治疗效果,可能与其降低Renin、AngⅡ及ALD水平,调节肾素-血管紧张素-醛固酮系统有关。

Effect of nephrectomy on vascular renin gene expression and biosynthesis of vascular aldosterone

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.

Expression of Angiotensin Ⅱ Receptors in Aldosterone-producing Adenoma of the Adrenal Gland and Their Clinical Significance

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.

Endoplasmic Reticulum Stress-mediated Aldosterone-induced Apoptosis in Vascular Endothelial Cells

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.

Combined Effects of Blood Pressure and Aldosterone on Cardiac Left Ventricular Mass Index—Ethnic Differences between Kazakh, Uygur and Han Subjects

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.

A novel bead-based fluorescence immunoassay for aldosterone

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.

Potential benefits of quinoxaline 1, 4-dioxides in aldosterone dysmetabolism disease—A medical hypothesis

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.

Angiotensin receptor blocker drugs and inhibition of adrenal beta-arrestin-1-dependent aldosterone production: Implications for heart failure therapy

Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II(Ang II). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure(HF), is induced by Ang II type 1 receptors(AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal through β-arrestin-1(βarr1) or-2(βarr2), both of which mediate G protein-independent signaling. Over the past decade, a second, Gq/11 proteinindependent but βarr1-dependent signaling pathway emanating from the adrenocortical AT1R and leading to aldosterone production has become appreciated. Thus, it became apparent that AT1R antagonists that block both pathways equally well are warranted for fully effective aldosterone suppression in HF. This spurred the comparison of all of the currently marketed angiotensin receptor blockers(ARBs, AT1R antagonists or sartans) at blocking activation of the two signaling modes(G protein-, and βarr1-dependent) at the Ang IIactivated AT1R and hence, at suppression of aldosterone in vitro and in vivo. Although all agents are very potent inhibitors of G protein activation at the AT1R, candesartan and valsartan were uncovered to be the most potent ARBs at blocking βarr activation by Ang II and at suppressing aldosterone in vitro and in vivo in post-myocardial infarction HF animals. In contrast, irbesartan and losartan are virtually G protein-"biased" blockers at the human AT1R, with very low efficacy for βarr inhibition and aldosterone suppression. Therefore, candesartan and valsartan(and other, structurally similar compounds) may be the most preferred ARB agents for HF pharmacotherapy, as well as for treatment of other conditions characterized by elevated aldosterone.

Effects of Continuous Positive Airway Pressure Therapy on Plasma Aldosterone Levels in Patients with Obstructive Sleep Apnea: A Meta-analysis

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.

Expression of Angiotensin Ⅱ and Aldosterone in Radiation-induced Lung Injury

Objective Radiation-induced lung injury （RILl） is the most common, dose-limiting complication in thoracic malignancy radiotherapy. Considering its negative impact on patients and restrictions to efficacy, the mechanism of RILl was studied. Methods Wistar rats were locally irradiated with a single dose of 0, 16, and 20 Gy to the right half of the lung to establish a lung injury model. Two and six months after irradiation, the right half of the rat lung tissue was removed, and the concentrations of TGF-[31, angiotensin II, and aldosterone were determined via enzyme-linked immunosorbent assay. Results Statistical differences were observed in the expression levels of angiotensin II and aldosterone between the non-irradiation and irradiation groups. Moreover, the expression level of the angiotensin II-aldosterone system increased with increasing doses, and the difference was still observed as time progressed. Conclusions Angiotensin II-aldosterone system has an important pathophysiological function in the progression of RILI.

Association of Polymorphisms in Angiotensin Ⅱ Receptor Genes with Aldosterone-producing Adenoma

This study examined the association of polymorphisms in angiotensinⅡreceptor genes（AT1R and AT2R） with the risk for aldosterone-producing adenoma（APA） in a Chinese Han population.Four polymorphisms including rs5182（573T/C） in exon 4,rs5186（1166A/C） in 3＇-untranslated region（3＇-UTR） in AT1R gene and rs5194（2274G/A） in 3＇-UTR,rs1403543（1675G/A） in intron 1 in AT2R gene were detected in 148 APA patients and 192 normal subjects（serving as control） by using a MGB-Taqman probe.The distribution of genotypes of each locus was in accordance with Hardy-Weinberg Equilibrium（HWE） in the APA and control groups（P0.05）.The allele A frequency at rs5194 was significantly higher in the APA group（0.49） than in the control group（0.35）（χ2=12.08,P=0.001）.Subjects with homozygotic genotype AA and heterozygotic genotype GA were at an increased risk for APA as compared to those with GG genotype（OR=2.66,95% CI=1.45-4.87;OR=1.67,95% CI=1.02-2.74）.Furthermore,rs5194 single-nucleotide polymorphism（SNP） at AT2R gene was significantly associated with APA in additive（OR=1.64,95% CI=1.21-2.20,P=0.001）,dominant（OR=1.94,95% CI=1.23-3.06,P=0.003）,and recessive model（OR=2.01,95% CI=1.17-3.45,P=0.01）.It was concluded that rs5194 polymorphism at AT2R gene was associated with the risk for APA,which may constitute a genetic marker of APA.

Isolated aldosterone deficiency in two infants: Mistakes and dilemmas in the diagnosis and treatment of a rare disease

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.

The Role of Ca^(2+) and Cyclic AMP in the Modulation of BenzodiazepineReceptor on Aldosterone Secretion

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 theCa2+ from extracellular Ca2+ pool, but not the Ca2+ from mitochondria Ca2+ pool or cAMP.

Advances in Medical Treatment of Primary Aldosteronism

Primary aldosteronism(PA)is the most common form of secondary hypertension,with its main manifestations including hypertension and hypokalemia.Early identification of PA is extremely important as PA patients can easily develop cardiovascular complications such as atrial fibrillation,stroke,and myocardial infarction.The past decade has witnessed the rapid advances in the genetics of PA,which has shed new light on PA treatment.While surgery is the first choice for unilateral diseases,bilateral lesions can be treated with mineralocorticoid receptor antagonists(MRAs).The next-generation non-steroidal MRAs are under investigations.New medications including calcium channel blockers,macrophage antibiotics,and aldosterone synthase inhibitors have provided a new perspective for the medical treatment of PA.

Difference in regulation mechanisms of ENaC by aldosterone and glucocorticords

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.

Effects of glucose and aldosterone on the proliferation of cardiac fibroblasts

Objective To investigate the effects of glucose and aldosterone on the proliferation of rat cardiac fibroblasts. Methods The neonatal SD rat cardiac fibroblasts （Cfs） were separated by the differential attachment technique. Cfs were incubated in different D- glucose concentrations for 24 hours, with or without aldosterone. DNA synthesis and metabolic activity of the Cfs were measured simultaneously with Brdu incorporation and WST-1 ELISA, respectively. Results Glucose at high concentrations （15 and 25 retool/L） significantly increased the proliferation of Cfs, compared with glucose at low concentration （5.6 retool/L, P〈0.01 ）, while no difference was shown on Cfs proliferation between the two high glucose concentration groups. Addition of aldosterone （10-Tmmol/L） to low- glucose media resulted in significant proliferation compared with those without aldosterone （WST- 1, P〈0.01; Brdu, P-4）.019）. However, when incubated in high glucose media, the stimulation effect of aldosterone for Cfs proliferation disappeared （P〉0.05）. Further analysis suggested that aldosterone have significant interaction on Cfs DNA synthesis （P=0.012）. Conclusions Both glucose and aldosterone could stimulate the proliferation of cultured Cfs. In high glucose concentration, the stimulatory effect for Cfs proliferation may be masked （J Geriatr Cardio12010; 7：36-39）.