Increased vascular responsiveness to bradykinin in kidneys of spontaneously hypertensive rats. Effect of N omega-nitro-L-arginine.
We investigated the role of nitric oxide (NO)-dependent and NO-independent mechanisms in mediation of renal vasodilatory responses to bradykinin in spontaneously hypertensive rats (SHR), rats with angiotensin II-induced hypertension (200 ng/min i.p. for 6 days) and the corresponding normotensive control Wistar-Kyoto (WKY) rats and sham-infused rats. To this end, we contrasted the effects of arterial injections of bradykinin and other vasodilators, acetylcholine and sodium nitroprusside, on perfusion pressure and output of cyclic GMP in isolated kidneys perfused with Krebs bicarbonate buffer containing phenylephrine, both with and without N omega-nitro-L-arginine (L-NOARG) (50 microM), an inhibitor of NO synthetase. In kidneys perfused without L-NOARG, all agonists increased the output of cyclic GMP and reduced perfusion pressure, indicative of vasodilation. In kidneys perfused with L-NOARG, vasodilatory responses to bradykinin and acetylcholine were attenuated, and associated effects on output of cyclic GMP were abolished, suggesting dependency on NO synthesis. Irrespective of whether kidneys were perfused with or without L-NOARG, kidneys of SHR were more responsive than kidneys of WKY rats with regard to bradykinin-induced vasodilation. In contrast, vasodilatory responsiveness to bradykinin was nearly equal in perfused kidneys of rats with angiotensin II-induced hypertension and in normotensive controls. Also, vasodilatory responsiveness to acetylcholine and sodium nitroprusside was similar in kidneys of normotensive and hypertensive rats. These data suggest that the renal vasculature of SHR is uniquely and selectively hyperresponsive to bradykinin, with regard to both the NO-dependent and NO-independent vasodilatory actions.
Cachofeiro
V
V
Department of Pharmacology, New York Medical College, Valhalla 10595.
Nasjletti
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects*
D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP; D000109:Acetylcholine; D001920:Bradykinin