Hypertension. 2005;45:270-275
Published online before print December 13, 2004,
doi: 10.1161/01.HYP.0000151622.47814.6f
(Hypertension. 2005;45:270.)
© 2005 American Heart Association, Inc.
Renal Angiotensin II Type-2 Receptors Are Upregulated and Mediate the Candesartan-Induced Natriuresis/Diuresis in Obese Zucker Rats
Amer C. Hakam;
Tahir Hussain
From the Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Texas.
Correspondence to Tahir Hussain, PhD, Assistant Professor of Pharmacology, Department of Pharmacological and Pharmaceutical Sciences, Science and Research Building 2, University of Houston, 4800 Calhoun, Houston, TX 77204-5037. E-mail thussain2{at}uh.edu
Recently, there has been a growing interest in studying the role of angiotensin II type-2 (AT2) receptor in renal/cardiovascular function in pathological conditions. The present study was designed to determine the functional role of the AT2 receptors on natriuresis/diuresis and compare the level of the tubular AT2 receptor expression in obese and lean Zucker rats (12 weeks old). Under anesthesia, candesartan (angiotensin II type 1 [AT1]–specific antagonist; 100 µg/kg bolus) produced natriuresis/diuresis to a greater degree in obese than in lean rats. The specific AT2 antagonist PD123319 (50 µg/kg per minute) after candesartan administration abolished the natriuretic/diuretic effects of candesartan in obese rats but not in lean rats. Infusion of AT2 receptor agonist, CGP-42112A (1 µg/kg per minute), produced greater increase in sodium and urine excretion over basal in obese than in lean rats. The presence of the AT2 receptor expression in the brush-border and basolateral membranes was confirmed by Western blotting using specific antibody and antigen-blocking peptide. Densitometric analysis of the bands revealed 
1.5- to 2.0-fold increase in the AT2 receptor proteins in both membranes of obese compared with lean rats. Our results suggest upregulation of the AT2 receptors, which play a role in mediating the natriuretic/diuretic effects of AT1 receptor blockers in obese Zucker rats. We speculate that AT2 receptors, by promoting sodium excretion, may protect obese Zucker rats against blood pressure increase associated with sodium and water retention.
Key Words: angiotensin II receptors • obesity • angiotensin II • kidney • angiotensin I • rats, Zucker
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