Role of AT2 receptor in long‐term blood pressure control in obese Zucker rat

Abstract

Earlier, we reported that there was an increase in angiotensin II AT2 receptor expression in the renal proximal tubule, and selective activation of the AT2 receptor by agonist inhibits Na,K‐ATPase activity and increases urinary Na excretion in obese Zucker rats. We hypothesized that AT2 receptor has a protective role against blood pressure increase in obese Zucker rats. To test this hypothesis, we treated obese Zucker rats with the AT2 receptor antagonist PD123319 (30 μg/kg/min) or AT2 receptor agonist CGP42112A (1 μg/kg/min) using osmotic pumps. Age‐matched lean and vehicle treated obese Zucker rats served as controls. On day 15 of the treatment with PD and CGP, mean arterial blood pressure (MAP) was measured by cannulation of the left carotid artery. Control obese rats exhibited higher MAP (122±3) versus lean control rats (97±5). The PD‐treatment of obese rats further raised MAP by 13 mmHg and CGP‐treatment decreased the MAP by 11mmHg. Western blot analysis revealed that the PD‐treatment in obese rats caused ~3‐fold increase in the renin expression in the kidney cortex, but had no effect on the expression of the cortical AT1 and AT2 receptors. The present study suggests that the AT2 receptors play a significant role in long‐term blood pressure regulation in obese Zucker rats, and this regulation, in part, could be due to the ability of the AT2 receptors to keep the kidney renin expression low in obese rats (NIH R01‐DK‐61578).