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

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Abstract
The effects of l‐NG‐nitro‐arginine (l‐NOARG) and some other arginine analogues on non‐adrenergic, non‐cholinergic (NANC) relaxations of the rat anococcygeus muscle were investigated. l‐NOARG (5–200 μm) produced concentration‐related inhibition of the NANC response; 100 μm l‐NOARG produced 90% inhibition. 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). l‐NG‐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‐NG‐monomethyl‐arginine (l‐NMMA). Like l‐NOARG, the effects of l‐NAME (20 μm) were reversed by 100 μm l‐ but not d‐arginine. Neither l‐NOARG nor l‐NAME (both 20 μm) affected submaximal relaxations induced by 10 μm sodium nitroprusside or 20 μm hydroxylamine. d‐NOARG, l‐NG‐tosyl‐arginine and l‐Nα‐(t‐butyl‐oxycarbonyl)‐NG‐nitroarginine (all at 100 μm) had no effect on NANC relaxations. 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.