title: Blockade of nitric oxide synthase potentiates the suppression of vasodilators by norepinephrine in the hepatic artery.
abstract: We have previously shown that nitric oxide (NO) and adenosine suppress vasoconstriction induced by norepinephrine infusion and sympathetic nerve stimulation in the hepatic artery and superior mesenteric artery. NO is involved in the control of basal vascular tone in the superior mesenteric artery but not the hepatic artery. The vasodilation induced by adenosine is inhibited by NO in the superior mesenteric artery but not in the hepatic artery. Based on these known interactions of catecholamines, adenosine, and NO, the objective of this study was to test the hypothesis that NO modulates the interaction between vasoconstrictors and vasodilators in the hepatic artery. We examined the ability of norepinephrine to suppress adenosine-mediated vasodilation and the role of NO in this interaction. Hepatic arterial blood flow and pressure were monitored in pentobarbital-anesthetized cats. The maximum hepatic arterial vasoconstrictor response to norepinephrine infusion was potentiated by blockade of NO production using Nomega-nitro-L-arginine methyl ester (L-NAME), and the potentiation was reversed by L-arginine. The maximum dilator response to adenosine was only slightly suppressed (14.0+/-5.8%, P < 0.05) by norepinephrine infusion; however, after the NO blockade, the suppression by norepinephrine of the vasodilation induced by adenosine was substantially potentiated (45.2+/-9.1%, P < 0.05). Similar results were obtained for isoproterenol-induced vasodilation. We conclude that the interaction between these vasodilators and norepinephrine was modulated by NO which inhibited the vasoconstriction and the suppression of vasodilators caused by norepinephrine and that in the absence of NO production, norepinephrine-induced constriction and the ability to antagonize dilation is substantially potentiated.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Han
authors.forename: W W
authors.initials: WW
authors.lastname: Lautt
mesh_terms: D000241:Adenosine / Q000037:antagonists & inhibitors; D000818:Animals; D002415:Cats; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006499:Hepatic Artery / Q000378:metabolism*; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009638:Norepinephrine / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D019001:Nitric Oxide Synthase; D000241:Adenosine; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine