ALDOSTERONE, ANGIOTENSIN II AND SYMPATHETIC ACTIVATION IN HYPERTENSIVES

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。体重增加是高血压的重要危险因素。体重增加和高血压均独立增加心血管发病率和死亡率的风险。肥胖和高血压之间的联系机制尚不清楚，尽管增加了交感神经对肌肉和肾脏的运输。尽管血浆醛固酮和血管紧张素II升高被认为起主要作用，但肥胖和高血压中交感神经活动增加的效应物仍缺乏特征性。 因此，我们计划进行一项随机、双盲、交叉研究，比较醛固酮阻滞剂的作用（用依普利酮），血管紧张素II阻断剂（与坎地沙坦西酯，以下仅称为坎地沙坦），联合醛固酮和血管紧张素II阻断（使用依普利酮和坎地沙坦），以及不含醛固酮或血管紧张素II拮抗剂的抗高血压药（氢氯噻嗪），用于患有和不患有高血压的肥胖和消瘦患者。次要结局指标包括绝对肌肉交感神经活性、皮肤和总前臂血流量、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.