Angotensin II Type 2 Receptors Participate in Reducing Blood Pressure During Angiotensin II Type 1 Receptor Blockade But Do not Affect Cardiovascular Mass and Coronary Hemodynamics
This study was designed to determine the role of AT2 receptors in the beneficial cardiovascular effects of chronic AT1 antagonism in spontaneously hypertensive rats (SHR). A selective AT1 receptor antagonist, candesartan (10mg/kg/day) alone (CAND), or in combination with the selective AT2 receptor antagonist PD 123319 (50g/kg/day) (CAND+PD) was given for 12 weeks to adult male SHR. Control SHR received placebo (PLACEBO) for the same period. Left ventricular coronary blood flow (CBF), flow reserve (CFR) and minimal coronary vascular resistance (MCVR) were measured using radiomicrospheres in 35-week old rats. Mean arterial pressure (MAP), peripheral resistance (TPR), left ventricular weight (LVI), and aortic weight (AWI)were also measured. The grater MAP in CAND+PD group compared with CAND suggests that AT2 receptor stimulation was responsible, in part for the hypotensive effect of AT1 receptor antagonism, although they did not contribute to improved coronary hemodynamics and reduced LV and aortic masses after selective AT1 receptor inhibition.