l‐NG‐monomethyl arginine andl‐NG‐nitro arginine inhibit non‐adrenergic, non‐cholinergic relaxation of the mouse anococcygeus muscle

The effects of L-NG-monomethyl arginine (L-NMMA) and L-NG-nitro arginine (L-NOARG) on non-adrenergic, non-cholinergic (NANC) relaxations of the mouse anococcygeus were investigated. 2. L-NMMA (10-200 microM) produced a concentration-related inhibition of the NANC response; the inhibitory effect of 50 microM L-NMMA was completely reversed by L-arginine but not D-arginine (both 100 microM). 3. L-NOARG (1-50 microM) also produced a concentration-related inhibition of the NANC response and was some 30-50 times more potent than L-NMMA; again, the effects of 10 microM L-NOARG were reversed by 100 microM L-, but not D-, arginine. By itself 100 microM L-arginine did not relax the tissue, but did cause a slight potentiation of the NANC response. 4. Sodium nitroprusside (0.01-10 microM), hydroxylamine (0.1-100 microM), sodium azide (1-100 microM) and nitric oxide (3-120 microM) all relaxed carbachol-induced tone; relaxations to submaximal concentrations of these nitrovasodilators were unaffected by either 50 microM L-NMMA or 10 microM L-NOARG. 5. L-NOARG 10 microM did not inhibit, but rather potentiated, contractions of the mouse anococcygeus due to stimulation of its sympathetic nerves. 6. The inhibitory effects of 10 microM L-NOARG on NANC relaxations were reversed by L-arginine (by 131%), L-citrulline (by 75%), L-arginine methyl ester (by 46%) and L-homoarginine (by 22%), but were unaffected by a variety of other amino acids and their derivatives (all at 100 microM). 7. The results provide strong evidence that NANC relaxations of the mouse anococcygeus are mediated by an endogenous nitrate material, probably derived from L-arginine, and confirm that L-NOARG provides a very useful and potent drug for the investigation of endogenous nitrate function.