Effect of N-G-nitro-L-arginine methyl ester on functionally characterized muscarinic receptors in anesthetized cats

This study was undertaken to determine if the nitric oxide (NO) synthase inhibitor, N-G-nitro-L-arginine methyl ester (L-NAME), is a competitive antagonist of muscarinic receptors in vivo. Cats were anesthetized with pentobarbital (36 mg/kg, i.p.). Five peripheral muscarinic responses were characterized based on their sensitivity to intravenous administration of atropine (1-100 mu g/kg), pirenzepine (1-100 mu g/kg) or gallamine (30-3000 mu g/kg) as follows: (1)muscarinic ganglionic transmission through the superior cervical ganglion to the nictitating membrane (M-1), (2) electrically elicited vagal bradycardia (M-2), (3) neurally evoked sudomotor responses (M-3; non-endothelial), (3) basal pupil tone in sympathectomized cats (M-3; non-endothelial) and (5) methacholine-induced depression of arterial blood pressure (M-3; endothelial). Additional groups of animals were administered L-NAME (50 mg/kg, i.v.) to determine if this agent would alter activation of these muscarinic systems. L-NAME was devoid of effect on responses elicited by stimulation of muscarinic M-1, M-2 and M-3 (non-endothelial) receptors. In contrast, L-NAME significantly reduced the depressor responses to i.v. methacholine (M-3; endothelial), as did its non-alkyl ester congener, L-NA (N-G-nitro-L arginine; 25 mg/kg, i.v.). These results support the conclusion that although L-NAME inhibits synthesis of nitric oxide in vascular endothelial cells, it is not a generalized muscarinic receptor antagonist in vivo. (C) 1997 Elsevier Science B.V.