POSSIBLE PHYSIOLOGICAL-ROLE OF ANGIOTENSIN II-(SUBTYPE AT(2))-RECEPTORS IN ISCHEMIC RAT HEARTS AND BOVINE AORTIC ENDOTHELIAL-CELLS

In isolated rat hearts the duration of postischemic ventricular fibrillations were reduced by the angiotensin II-(subtype AT(1))-receptor antagonist S0029 (10(-6) mol/l). Go-perfusion with angiotensin II (ANG II, 10(-10) mol/l) nearly completely protected the hearts against ventricular fibrillations. The protective effect of S0029 was abolished by either the B-2 kinin receptor antagonist icatibant (HOE 140) or the NO synthase inhibitor N-G-nitro-1-arginine (L-NNA). Perfusion with the ANG II-(subtype AT(2))receptor antagonist CGP 42112A aggraveted the duration of ventricular fibrillation in contrast to S0029. In bovine aortic endothelial cells ANG II (10(-7)-10(-4) mol/l) stimulated intracellular cyclic GMP (cGMP) production. This stimulation could be suppressed by preincubation with icatibant or L-NNA. CGP 42112A led to about 60% inhibition (IC50 = 3 x 10(-10) mol/l) of the ANG II induced stimulation, whereas S0029 was effective only in higher concentrations (IC50 = 3 x 10(-5) mol/l). After blocking the AT(1) receptor in the rat heart stimulation of a high affinity subtype-AT(2)-receptor via endogeneous ANG-II seems to induce the enhanced production and release of endothelial derived kinins with subsequent synthesis of NO and cGMP. One of these mediators might explain the reduction in postischemic ventricular fibrillations.