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.

ALD法制备Li掺杂NiO_(x)作为HTL提升PSC性能

空穴传输层(HTL)是影响钙钛矿太阳能电池性能的主要因素之一。氧化镍(NiO_(x))是广为关注的无机HTL材料。原子层沉积(ALD)法具有厚度精准控制、台阶覆盖性好、薄膜质量高等优势,采用ALD法制备了不同比例锂(Li)掺杂的NiO_(x)薄膜。结果显示ALD法制备的NiO_(x)薄膜具有较小的均方根表面粗糙度、较高的光学透过率、较大的禁带宽度,而合适的Li掺杂量可以调制其与钙钛矿吸收层之间的能带匹配,这有利于获得更高的开路电压与短路电流。最终,以Li与NiO_(x)掺杂比为1∶500的NiO_(x)薄膜作为HTL制备了电池器件,开路电压高达1.14 V,短路电流为21.73 mA/cm^(2),填充因子为80.5%,光电转换效率为19.95%,这在宽带隙倒置钙钛矿电池中是一个不错的水平。

基于网络药理学和分子对接技术研究西河柳化学成分治疗ALD的作用机制

目的:通过网络药理学和分子对接技术分析西河柳中有效化学成分治疗酒精性肝病的作用机制。方法:通过TCMSP平台检索西河柳活性化学成分及作用靶点,并以口服利用度≥30%和类药性≥0.18为预设条件对其进行筛选;同时,使用GeneCards、DrugBank等数据库,筛选ALD相关靶点。通过VennDiagram软件可以获得一个交集靶点(西河柳和ALD);通过疾病、中药活性成分、交集靶点形成数据网络,最终遴选出致病的核心靶点进行分子结构处理和分子对接;进行GO功能富集和KEGG通路注释分析;结果由R语言和Perl语言进行可视化。结果:筛选获得槲皮素、山奈酚、异鼠李素等西河柳的主要活性化学成分,西河柳与酒精性肝病交集靶点共151个,GO功能富集分析得105条,KEGG通路筛选得129条信号通路。结论:本研究初步揭示了西河柳可通过多化学成分、多靶点、多通路治疗ALD,为天然药用植物的开发和利用提供了理论参考。

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.

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。

沙库巴曲缬沙坦对慢性心力衰竭患者AngⅡ、ALD、NT-proBNP水平及心功能的影响

目的:探究沙库巴曲缬沙坦对慢性心力衰竭(CHF)患者血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)、N末端B型利钠肽前体(NT-proBNP)水平及心功能的影响。方法:选取2021年1月—2023年1月荆州市第三人民医院收治的65例CHF患者为研究对象。根据随机抽签法将其分为对照组(32例)与观察组(33例)。对照组给予缬沙坦片,观察组给予沙库巴曲缬沙坦钠片。比较两组治疗前及治疗6个月后实验室指标、生活质量及心功能。结果:治疗6个月后,两组AngⅡ、ALD、NT-pro BNP水平均下降,观察组AngⅡ、ALD、NT-pro BNP水平均低于对照组,差异有统计学意义(P<0.05)。治疗6个月后,两组左心室射血分数(LVEF)升高,左心室收缩期内径(LVESD)及左心室舒张期内径(LVEDD)均降低,观察组LVEF显著高于对照组,LVESD、LVEDD显著低于对照组,差异有统计学意义(P<0.05)。治疗6个月后,两组身体、情绪及其他评分均下降,观察组身体、情绪及其他评分均低于对照组,差异有统计学意义(P<0.05)。结论:沙库巴曲缬沙坦治疗CHF患者,可降低AngⅡ、ALD、NT-proBNP水平,减轻心脏负荷,改善患者心功能,促进生活质量提高。

急性心肌梗死患者PCI术后近期预后不良的高危因素及Hcy、CysC、AngⅡ、ALD、BNP的预测价值

目的探讨急性心肌梗死(AMI)患者皮冠状动脉介入治疗(PCI)术后近期预后不良的高危因素及血清同型半胱氨酸(Hcy)、胱抑素(CysC)、血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)、脑钠肽(BNP)对其预测价值。方法回顾性分析2020年6月至2023年1月收治的214例AMI患者临床资料,患者出院后随访6个月,根据随访后患者预后情况分为预后良好组(n=170)和预后不良组(n=44例)。比较2组临床资料,采用单因素及多因素分析法分析AMI患者PCI术后近期预后不良的高危因素;分别采用酶循环法、乳胶免疫比浊法、化学发光法、直接化学发光法检测血清Hcy、CysC、AngⅡ、ALD、BNP表达水平;采用受试者工作特征曲线(ROC)分析Hcy、CysC、AngⅡ、ALD、BNP单独及联合检测对AMI患者PCI术后近期预后不良的诊断价值。结果AMI患者PCI术后近期预后不良44例,发生率为20.56%(44/214)。多因素Logistic回归分析结果显示,心功能分级≥Ⅱ级、术前心搏骤停、病变血管有3支、血浆胆红素水平高均是AMI患者PCI术后近期预后不良的高危因素(OR=2.113,2.008,2.273,2.143,P<0.05)。预后不良组血清Hcy、CysC、AngⅡ、ALD、BNP水平均显著高于预后良好组(P<0.05)。绘制ROC曲线获得Hcy、CysC、AngⅡ、ALD、BNP单独及联合检测诊断AMI患者PCI术后近期预后不良的曲线下面积(AUC)分别为0.777、0.765、0.656、0.721、0.756、0.943;其中,联合诊断的AUC高于各项单独检测,Hcy高于AngⅡ,且联合检测的敏感度和特异度为93.20%,80.00%。结论AMI患者PCI术后近期预后不良发生率较高,AMI患者PCI术后近期预后不良的Hcy、CysC、AngⅡ、ALD、BNP呈高表达,联合检测Hcy、CysC、AngⅡ、ALD、BNP有助于诊断AMI患者PCI术后近期预后不良,且AMI患者PCI术后近期预后不良的发生与心功能分级、术前心搏骤停、病变血管有3支、血浆胆红素水平密切相关。

ALD反应沉积超薄TiO_(2)改性LiNi_(0.8)Co_(0.1)Mn_(0.1)O_(2)正极材料及其电化学性能

高镍三元正极材料LiNi_(x)Co_(y)Mn_(1-x-y)O_(2)(NCM,ω(Ni)60%)由于粉体颗粒表面的相变,电解液副产物HF的侵蚀,过渡金属离子的溶解等问题,其循环性能及安全稳定性一直不理想.通过原子层沉积(atomic layer deposition,ALD)反应在高镍Li Ni_(0.8)Co_(0.1)Mn_(0.1)O_(2)(NCM811)正极材料表面均匀沉积了超薄Ti O_(2)涂层,用于改善其电化学性能.研究结果表明:通过ALD反应沉积Ti O_(2)后,改性NCM811的性能明显改善;超薄Ti O_(2)涂层阻碍了NCM811活性颗粒与电解液的直接接触,提高了材料的循环稳定性;在循环过程中,超薄涂层不会影响锂离子的传输.通过ALD反应沉积超薄涂层为改性电极材料提供了新思路.

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.

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.