Coronary hemodynamic and ventricular responses to angiotensin type 1 receptor inhibition in SHR - Interaction with angiotensin type 2 receptors

This study was designed to determine the effects of angiotensin II type 1 ( AT(1)) receptor inhibition on coronary hemodynamics and ventricular mass an d hydroxyproline content and the additive effects of angiotensin II type 2 (AT(2)) receptor inhibition in spontaneously hypertensive rats (SHR). The s elective AT(1) receptor antagonist candesartan (10 mg/kg per day) was admin istered alone or in combination with the AT(2) receptor antagonist PD 12331 9 (50 mg/kg per day) for 12 weeks. Control SHR received placebo for the sam e period. Left and right ventricular coronary blood flow, blood flow reserv e, and minimal coronary vascular resistance were determined by using radiom icrospheres in male 35-week-old rats. Mean arterial pressure; total periphe ral resistance; left and right ventricular, renal, and aortic weights; and hydroxyproline concentration were also determined. Candesartan reduced mean arterial pressure and left ventricular, renal, and aortic masses, as well as hydroxyproline concentration and minimal coronary vascular resistance of both ventricles. PD 123319 partially prevented the hypotensive effect of A T(1) receptor inhibition and reversed the effect on myocardial hydroxyproli ne concentration. These data suggest that AT(2) receptors contribute to the hypotensive and antifibrotic effects but not the coronary hemodynamic impr ovement or reduced left ventricular mass of AT(1) receptor inhibition in th ese adult SHR.