THE INHIBITORY EFFECT OF ANGIOTENSIN-II ON STIMULUS-INDUCED RELEASE OF CAMP IS AUGMENTED IN THE GENETICALLY HYPERTENSIVE RAT-KIDNEY

In the present study, with isolated perfused kidneys, we evaluated whe ther angiotensin II (Ang II) inhibits stimulus-induced release of aden osine 3',5'-cyclic monophosphate (cAMP) and whether this effect is aug mented in spontaneously hypertensive rats (SHR). The basal release of cAMP (in venous effluent) in the presence of captopril (1 mu mol/l) an d a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (10 mu mo l/l), was significantly (P < .05) higher in the SHR (n = 20) than in W istar-Kyoto (WKY) kidneys (n = 18) although perfusion pressures were n ot significantly different in the two strains. Isoproterenol infusions (ISO; 0.3, 1 and 3 mu mol/l) significantly and similarly increased cA MP release in both WKY (n = 5; P < .01) and SHR (n = 6; P < .01) kidne ys. A time-related attenuation of the cAMP response to ISO in both str ains 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 a nd 10 ng/min). In the same experiments, ISO produced small but signifi cant 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; how ever, Ang II exerts a much greater negative influence on the ISO-induc ed increases in cAMP levels in the renal vasculature of SHR. The augme nted inhibition of stimulus-induced cAMP release may be associated wit h an increased renovascular responsiveness to Ang II in SHR.