ALDOSTERONE, ANGIOTENSIN II AND SYMPATHETIC ACTIVATION IN HYPERTENSIVES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。体重增加是高血压的一个重要危险因素。体重增加和高血压各自增加心血管疾病发病率和死亡率的风险。肥胖和高血压之间关联的机制尚不清楚，尽管已经涉及到肌肉和肾脏交感神经流量的增加。尽管血浆醛固酮和血管紧张素II升高被认为起主要作用，但肥胖和高血压患者交感神经活动增加的效应物仍不清楚。因此，我们计划进行一项随机、双盲、交叉研究，比较醛固酮拮抗剂（与依普利酮联合使用）、血管紧张素II拮抗剂（与坎地沙坦西列地酯联合使用，以下简称坎地沙坦）、醛固酮和血管紧张素II联合拮抗剂（同时使用依普利酮和坎地沙坦）以及一种不具有醛固酮或血管紧张素II拮抗剂（氢氯噻嗪）在肥胖和无高血压患者中的作用。次要结局指标包括绝对肌肉交感神经活动、皮肤和前臂总血流量、骨骼肌氧合、内皮功能、心输出量和各种神经内分泌介质的水平。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Increased body mass is an important risk factor for hypertension. Both increased body mass and hypertension independently increase the risk of cardiovascular morbidity and mortality. The mechanisms responsible for the association between obesity and hypertension remain unclear although increased sympathetic nerve traffic to muscles and the kidneys has been implicated. The effectors responsible for the increased sympathetic neural activity in obesity and hypertension remain poorly characterized although elevated plasma aldosterone and angiotensin II are believed to play a major role. We therefore plan to conduct a randomized, double blind, crossover study comparing the effects of aldosterone blockade (with eplerenone), angiotensin II blockade (with candesartan cilexetil, hereafter referred to only as candesartan), combined aldosterone and angiotensin II blockade (using both eplerenone and candesartan), and an antihypertensive agent without aldosterone or angiotensin II antagonism (hydrochlorothiazide) in obese and lean patients with and without hypertension. The secondary outcome measures include the absolute muscle sympathetic nerve activity, skin and total forearm blood flow, skeletal muscle oxygenation, endothelial function, cardiac output, and levels of various neuroendocrine mediators.