L‐NG‐nitro‐arginine and its methyl ester are potent inhibitors of non‐adrenergic, non‐cholinergic transmission in the rat anococcygeus

Abstract

1 The effects of l-N^G-nitro-arginine (l-NOARG) and some other arginine analogues on non-adrenergic, non-cholinergic (NANC) relaxations of the rat anococcygeus muscle were investigated. 2 l-NOARG (5–200 μm) produced concentration-related inhibition of the NANC response; 100 μm l-NOARG produced 90% inhibition. 3 l-Arginine (5–200 μm) produced a concentration-related reversal of the inhibitory effect of 20 μm l-NOARG; a five fold excess of l-arginine (100 μm) was required to obtain the maximum reversal of 90%. d-Arginine (100 μm) produced no such reversal, but significant reversal was produced by l-citrulline, l-arginine-l-aspartate, l-homoarginine and l-arginine-methyl-ester (all at 100 μm). 4 l-N^G-nitro-arginine-methyl-ester (l-NAME; 5–200 μm) also reduced NANC relaxations, with a potency similar to that of l-NOARG; both l-NOARG and l-NAME were some ten times more potent than l-N^G-monomethyl-arginine (l-NMMA). Like l-NOARG, the effects of l-NAME (20 μm) were reversed by 100 μm l- but not d-arginine. 5 Neither l-NOARG nor l-NAME (both 20 μm) affected submaximal relaxations induced by 10 μm sodium nitroprusside or 20 μm hydroxylamine. 6 d-NOARG, l-N^G-tosyl-arginine and l-N^α-(t-butyl-oxycarbonyl)-N^G-nitroarginine (all at 100 μm) had no effect on NANC relaxations. 7 Thus, in the rat anococcygeus, l-NOARG and l-NAME are more potent than l-NMMA as prejunctional inhibitors of NANC transmission. The reversibility of the effect of l-NOARG by arginine analogues suggests that the NANC system of the anococcygeus shows similarities to the endogenous nitrate system recently described in the brain.