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

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 μ m ) produced concentration‐related inhibition of the NANC response; 100 μ m l ‐NOARG produced 90% inhibition. 3 l ‐Arginine (5–200 μ m ) produced a concentration‐related reversal of the inhibitory effect of 20 μ m l ‐NOARG; a five fold excess of l ‐arginine (100 μ m ) was required to obtain the maximum reversal of 90%. d ‐Arginine (100 μ m ) 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 μ m ). 4 l ‐N G ‐nitro‐arginine‐methyl‐ester ( l ‐NAME; 5–200 μ m ) 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 μ m ) were reversed by 100 μ m l ‐ but not d ‐arginine. 5 Neither l ‐NOARG nor l ‐NAME (both 20 μ m ) affected submaximal relaxations induced by 10 μ m sodium nitroprusside or 20 μ m hydroxylamine. 6 d ‐NOARG, l ‐N G ‐tosyl‐arginine and l ‐N α ‐( t ‐butyl‐oxycarbonyl)‐N G ‐nitroarginine (all at 100 μ m ) 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.