Protective Role of Angiotensin II Subtype 2 Receptor in Blood Pressure Increase in Obese Zucker Rats

Abstract

Earlier, we reported that there was an increase in angiotensin II type 2 (AT 2 ) receptor expression in the renal proximal tubule, and selective activation of the AT 2 receptor by AT 2 agonist inhibits Na,K-ATPase activity in the proximal tubules and increases urinary Na excretion in obese Zucker rats. We hypothesized that the AT 2 receptor has a protective role against blood pressure increase in obese Zucker rats. To test this hypothesis, we treated obese Zucker rats with the AT 2 receptor antagonist PD123319 (PD; 30 μg/kg per minute) using osmotic pumps. Age-matched lean rats and vehicle-treated obese Zucker rats served as controls. On day 15 of the treatment with PD, arterial blood pressure was measured by cannulation of the left carotid artery under anesthesia. Control obese rats exhibited higher mean arterial pressure (122.0±3.4 mm Hg) compared with lean control rats (97.0±4.8 mm Hg). The PD treatment of obese rats raised mean arterial pressure further by 13 mm Hg. The plasma renin activity was significantly increased in the PD-treated obese compared with control-obese or lean rats. Western blot analysis revealed that the PD treatment in obese rats caused an ≈3-fold increase in the renin expression in the kidney cortex but had no effect on the expression of the cortical angiotensin II type 1 and AT 2 receptors. The present study suggests that the renal AT 2 receptors provide a protective role against blood pressure increase in obese Zucker rats, and this protective effect, in part, could be because of the ability of the AT 2 receptors to keep the kidney renin expression low in obese rats.