We studied the functional role of angiotensin II (AII) receptor subtypes and vasodilatory endothelial autacoid release in response to AII in isolated perfused rabbit hearts. AII infusion induced biphasic changes in coronary perfusion pressure (CPP): an initial increase was followed by a decrease until a plateau was reached. At higher concentrations of AII (> or = 10 nmol/l) this plateau phase was lower than the initial CPP level. AII infusion elicited inverse changes in peak left ventricular pressure (LVP): coronary constriction was associated with a transient decline, and during the plateau phase LVP was clearly increased. AII also moderately augmented prostacyclin (PGI2) release from the coronary vascular bed. The AII-induced changes in CPP, LVP, and PGI2 release were effectively inhibited by the AT1 receptor subtype antagonist ICI D8731 (30 nmol/l), but not by the AT2 receptor antagonist CGP 42112 (30 nmol/l). The adenosine A1 receptor antagonist 8-phenyltheophylline (0.1 mumol/l) attenuated the decline in CPP following the constriction phase without affecting the changes in LVP during AII infusion. The cyclooxygenase inhibitor diclofenac (1 mmol/l) had no effect on the AII-induced changes in CPP, whereas the nitric oxide-synthase inhibitor NG-nitro-L-arginine (30 mumol/l) markedly potentiated the vasoconstriction but was without effect on the plateau phase of the response. In contrast to AII, the thromboxane analogue U46619 elicited sustained increases in CPP which were associated with slight decreases in LVP.(ABSTRACT TRUNCATED AT 250 WORDS)