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, NG-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 microg/kg), pirenzepine (1-100 microg/kg) or gallamine (30-3000 microg/kg) as follows: (1) muscarinic ganglionic transmission through the superior cervical ganglion to the nictitating membrane (M1), (2) electrically elicited vagal bradycardia (M2), (3) neurally evoked sudomotor responses (M3; non-endothelial), (4) basal pupil tone in sympathectomized cats (M3; non-endothelial) and (5) methacholine-induced depression of arterial blood pressure (M3; 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 M1, M2 and M3 (non-endothelial) receptors. In contrast, L-NAME significantly reduced the depressor responses to i.v. methacholine (M3; endothelial), as did its non-alkyl ester congener, L-NA (NG-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.