Angiotensin II type 2 receptor blockade partially negates antihypertrophic effects of type 1 receptor blockade on pressure-overload rat cardiac hypertrophy.

Abstract

We investigated the effects of angiotensin II type 2 (AT2) receptor blockade on the antihypertrophic effects of type 1 receptor (AT1) blockade in pressure-overload cardiac hypertrophy in adult rats. Cardiac hypertrophy was induced by banding the abdominal aorta above the renal arteries. The rats were treated with either an AT1 receptor antagonist TCV-116 (TCV, 10 mg/kg/day), an AT2 receptor antagonist PD123319 (PD, 20 mg/kg/day), or both for 4 weeks after the aortic banding. We measured systolic and diastolic blood pressure (BP), body weight (BW), left ventricular weight (LVW), and serum and cardiac angiotensin converting enzyme (ACE) activities. Aortic banding increased BP and LVW/BW, and TCV reversed both these increases. PD affected neither BP nor LVW/BW. TCV+PD reversed the increase in BP but not LVW/BW. Thus, PD was considered to counteract the antihypertrophic effect of TCV without affecting BP. All three treatments reduced cardiac ACE activity without affecting serum ACE activity. Our data demonstrated that AT2 receptor blockade negates the antihypertrophic effects of AT1 receptor blockade in an adult rat model of pressure-overload cardiac hypertrophy. AT2 receptors may mediate the signaling pathways involved in growth inhibition, which could counteract mediation of the cellular growth signaling pathways by AT1 receptors.