In the present study, with isolated perfused kidneys, we evaluated whether angiotensin II (Ang II) inhibits stimulus-induced release of adenosine 3',5'-cyclic monophosphate (cAMP) and whether this effect is augmented in spontaneously hypertensive rats (SHR). The basal release of cAMP (in venous effluent) in the presence of captopril (1 mumol/l) and a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (10 mumol/l), was significantly (P < .05) higher in the SHR (n = 20) than in Wistar-Kyoto (WKY) kidneys (n = 18) although perfusion pressures were not significantly different in the two strains. Isoproterenol infusions (ISO; 0.3, 1 and 3 mumol/l) significantly and similarly increased cAMP release in both WKY (n = 5; P < .01) and SHR (n = 6; P < .01) kidneys. A time-related attenuation of the cAMP response to ISO in both strains was observed in these experiments. In control experiments, Ang II (3 and 10 ng/min), by itself, did not significantly alter basal cAMP release in either strain but raised perfusion pressure in both SHR and WKY kidneys. In a separate set of experiments, Ang II significantly (3 ng/min: P < .05; 10 ng/min: P < .01) inhibited ISO-induced increases in release of cAMP from SHR kidneys (n = 8), whereas cAMP release in response to ISO in WKY kidneys (n = 8) was not affected by Ang II (3 and 10 ng/min). In the same experiments, ISO produced small but significant decreases in perfusion pressure in WKY (P < .01) but not in SHR. These data clearly and directly demonstrate that ISO-induced increases in cAMP in the renal vasculature are similar in SHR and WKY rats; however, Ang II exerts a much greater negative influence on the ISO-induced increases in cAMP levels in the renal vasculature of SHR. The augmented inhibition of stimulus-induced cAMP release may be associated with an increased renovascular responsiveness to Ang II in SHR.