L-NG-NITRO-ARGININE AND ITS METHYL-ESTER ARE POTENT INHIBITORS OF NONADRENERGIC, NONCHOLINERGIC TRANSMISSION IN THE RAT ANOCOCCYGEUS

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. 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 recuired 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-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. 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-N(G)-tosyl-arginine and L-N(α)-(t-butyl-oxycarbonyl)-N(G)-nitro-arginine (all at 100 μM) 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.