{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:45:17Z","timestamp":1789152317035,"version":"build-2803163510"},"reference-count":40,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2008,5]]},"abstract":"<jats:p>The obese Zucker rat reportedly has increased activity of the intrarenal renin-angiotensin-aldosterone system, which conceptually could contribute to elevated salt sensitivity and blood pressure (BP). Our aim was to determine whether there was increased angiotensin II type 1 receptor (AT<jats:sub>1<\/jats:sub>R)-mediated upregulation of expression or activity of the bumetanide-sensitive Na-K-2Cl cotransporter, the thiazide-sensitive Na-Cl cotransporter (NCC), and\/or the epithelial sodium channel (ENaC) in obese vs. lean Zucker rats. Male obese and lean Zucker rats (10-wk old) were fed either 1) control chow (1% NaCl) or 2) chow with candesartan (CAN), an AT<jats:sub>1<\/jats:sub>R antagonist (25 mg\/kg\u00b7diet) for 14 wk ( n = 8\/treatment\/body type). BP measured by radiotelemetry, was markedly reduced by CAN (\u223c20\u201325 mmHg) in both lean and obese rats with no body-type differences. Obese rats had significantly greater net natriuretic response to single injections of hydrochlorothiazide and benzamil, suggesting increased activity of NCC and ENaC, respectively; however, only the response to benzamil was reduced by CAN. CAN led to a significant reduction in whole kidney levels of NCC and \u03b3-ENaC (70-kDa band) in both lean and obese rats. However, it significantly increased \u03b1-ENaC and Na-K-2Cl cotransporter levels, and these increases were greater in obese rats. These studies suggest that relatively increased ENaC, but not NCC activity, in obese rats is due to enhanced AT<jats:sub>1<\/jats:sub>R activity. CAN attenuated the reduction of several renal transporters in the obese rat kidney. Finally, differences in intrarenal AT<jats:sub>1<\/jats:sub>R activity do not seem directly responsible for BP differences between lean and obese rats.<\/jats:p>","DOI":"10.1152\/ajprenal.00604.2007","type":"journal-article","created":{"date-parts":[[2008,2,28]],"date-time":"2008-02-28T02:00:34Z","timestamp":1204164034000},"page":"F1222-F1231","source":"Crossref","is-referenced-by-count":29,"title":["Chronic candesartan alters expression and activity of NKCC2, NCC, and ENaC in the obese Zucker rat"],"prefix":"10.1152","volume":"294","author":[{"given":"Veerendra K.","family":"Madala 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