THE EFFECTS OF PERFUSION RATE AND N-G-NITRO-L-ARGININE METHYL-ESTER ON CIRAZOLINE-INDUCED AND KCL-INDUCED RESPONSES IN THE PERFUSED MESENTERIC ARTERIAL BED OF RATS

1 The purpose of this study was to characterize the effects of NG-nitro-L-arginine methyl ester (L-NAME) on the perfusion rate/pressure relations, and on the presser responses induced to cirazoline and KCI in isolated, perfused mesenteric arterial beds from normotensive and spontaneously hypertensive rats. 2 The basal perfusion pressure of arterial beds perfused with either physiological salt solution (PSS) or PSS containing 1% polyvinylpyrrolidone increased as the perfusion rate increased. L-NAME, in concentrations up to 100 mu M, failed to alter the basal pressure regardless of the perfusion rate and viscosity; however, at 5 mu M, it potentiated cirazoline-induced vasoconstriction at each of the perfusion rates. 3 L-NAME but not D-NAME caused a leftward shift of cirazoline concentration-response curves with a marked increase in the maximal response. The potentiating action of L-NAME was abolished in arterial beds perfused with a Ca2+-free physiological salt solution and also in beds denuded of endothelium by an infusion of distilled water for 5 min. 4 In endothelium-intact and -denuded preparations, L-NAME potentiated KCI presser responses; the endothelium-independent potentiation of KCl presser activity was stereospecific, time-independent and was not prevented by the presence of dexamethasone (0.5 mu M) in the perfusion medium. However, L-NAME failed to potentiate vasoconstriction obtained to KCI in arterial beds denervated by cold storage (4-5 degrees C) for 2 days. 5 The absence of K+ in the perfusate did not inhibit the ability of L-NAME to potentiate alpha-adrenoceptor-mediated presser responses, and nor did L-NAME inhibit KCl-induced vasodilatation in preconstricted arteries. It was thus concluded that L-NAME does not affect Na+/K+-ATPase activity. 6 No differences in the potentiating ability of L-NAME on either cirazoline- or KCl-mediated presser responses were apparent between normotensive Sprague Dawley (SD), Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. 7 Our data thus provide evidence that: the presence of a vasoconstrictor is required for basal nitric oxide (NO) release in the mesenteric arterial bed from either normotensive or spontaneously hypertensive rats; L-NAME causes potentiation of cirazoline- and KCl-induced vasoconstriction respectively by inhibiting endothelial and neuronal NO synthase(s). Furthermore, our data indicate that NO synthase activity is not impaired in the mesenteric arterial bed of spontaneously hypertensive rats.