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Cross‐talk between NAD(P)H oxidase and AT1 receptors in the proximal tubules of obese Zucker rats
Author(s) -
Sabuhi Rifat,
Siddiqui Athar,
Hussain Tahir
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.803.4
Subject(s) - apocynin , candesartan , endocrinology , natriuresis , medicine , angiotensin ii receptor type 1 , chemistry , diuresis , angiotensin ii , nad(p)h oxidase , nadph oxidase , receptor , kidney , oxidative stress
Abnormal regulation of renin‐angiotensin system and increased level of oxidative stress have been implicated in renal/cardiovascular diseases associated with obesity. Earlier, we have shown that Angiotensin II AT1 receptor activity causes greater antinatriuresis via enhanced stimulation of tubular Na,K‐ATPase (NKA) in obese Zucker rats. The present study investigated the role of NAD(P)H oxidase in the enhanced AT1 receptor function in obese Zucker rats. Lean and obese Zucker rats were given NAD(P)H oxidase inhibitor, apocynin (3.5 μg/kg/min; i.v infusion) and/or AT1 receptor antagonist, candesartan (100 μg/kg; i.v bolus). Pretreatment with apocynin completely abolished candesartan‐induced diuresis/natriuresis in obese Zucker rats. In lean Zucker rats, apocynin alone increased diuresis/natriuresis and had an additive effect on diuresis/natriuresis when given along with candesartan. The blood pressure and GFR remained unchanged during drug treatment indicating a tubular effect. Apocynin treatment abolished and brought the AngII‐stimulated NKA activity below the basal activity in the isolated proximal tubules of obese Zucker rats. The data suggest NAD(P)H oxidase as an antinatriuretic molecule that switches to AT1 receptor signaling in the proximal tubules of obese Zucker rats and thereby contributes to the enhanced antinatriuresis. (NIH‐R01‐DK‐61578; GEAR‐UH)