This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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