NOS inhibition potentiates norepinephrine but not sympathetic nerve-mediated co-transmission in resistance arteries

Objective: The in vitro interaction between sympathetic nerves and basal ni tric oxide release was studied in a resistance artery, since these interact powerfully in large vessels. Methods: The pharmacological interaction betw een L-NAME and vasoconstriction to field stimulation of sympathetic nerves or exogenous norepinephrine was studied in rabbit cutaneous resistance arte ries in wire myographs. Results: Relaxation of norepinephrine-induced tone by acetylcholine, but not sodium nitroprusside, was blocked by N-omega-nitr o-L-arginine methyl ester (L-NAME: 100 mu M), indicating that the agonist-i nduced release of nitric oxide could oppose the vasoconstrictor effect of n orepinephrine and confirming that L-NAME had no effect on endothelium-indep endent vasodilatation. L-NAME increased norepinephrine potency indicating b asal NO release. With short bursts of electrical field stimulation purinerg ic transmission was dominant at low frequencies and adrenergic at high freq uencies. L-NAME had no effect on nerve-mediated responses, even after block ing the purinergic component with alpha,beta-methylene ATP (3 mu M), sugges ting that the influence of spontaneously released nitric oxide does not ext end to the vascular smooth muscle cells under adrenergic nervous control. C onclusion(s): This resistance artery exhibits a highly effective nitric oxi de-mediated vasodilatation to acetylcholine. It has basal release of nitric oxide which antagonises exogenous norepinephrine. However, basal nitric ox ide did not influence adrenergic nerve transmission, which contrasts with p revious studies of larger arteries and veins. We speculate that in small re sistance arteries there may be a spatial limitation to the zones of vascula r smooth muscle influenced by the adrenergic nerves and by basal nitric oxi de from the endothelium, respectively. The role of endogenous nitric oxide in modulating vascular tone may thus be less in resistance arteries than in conducting arteries or capacitance vessels and purinergic transmission app ears to be particularly resistant. (C) 1999 Elsevier Science B.V. All right s reserved.