NORADRENERGIC-NITRERGIC INTERACTIONS IN THE RAT ANOCOCCYGEUS MUSCLE -EVIDENCE FOR POSTJUNCTIONAL MODULATION BY NITRIC-OXIDE

1 The distribution of NADPH-diaphorase positive and catecholamine-cont aining nerve structures, and functional noradrenergic-nitrergic intera ctions, were studied in the rat anococcygeus muscle. 2 The morphologic al findings demonstrated NADPH-diaphorase positive neurones mostly as aggregates in intramural ganglia, nerve tracts and few single nerve fi bres forming plexus-like structures. 3 The nitric oxide synthase inhib itor N-G-nitro-L-arginine (L-NOARG) inhibited concentration-dependentl y the nitrergic relaxation, an effect reversed by L-arginine. The drug had dual effects on noradrenergic contractile responses: at lower con centrations (0.1-10 mu M) it decreased the amplitude of contractions a nd this was not affected by L-arginine; higher concentrations (50-500 mu M) potentiated the contractions, an effect that was prevented by L- arginine. 4 The electron acceptor, nitro blue tetrazolium (NBT) produc ed a rapid inhibition of the noradrenergic contractile responses (EC(5 0) 0.178 +/- 0.041 mu M). The drug decreased the tone of the preparati ons. However, it potentiated concentration-dependently the nitrergic r elaxations. 5 NBT (1 mu M) had no significant effect on the relaxation s induced by exogenously applied nitric oxide (NO)-donor sodium nitrop russide (SNP, 0.01-50 mu M). However, the effect of NBT (0.1-10 mu M) On. the electrically induced relaxation was significantly decreased by L-NOARG (10 and 50 mu M). The inhibition was of a non-competitive typ e. 6 Neither L-NOARG (100 mu M) nor NBT (1 mu M) had any effect on the spontaneous or electricalIyinduced release of H-3-radioactivity from the tissues preincubated in [H-3]-noradrenaline. 7 It is concluded tha t L-arginine-NO pathway can modulate noradrenergic transmission in the rat anococcygeus muscle at postjunctional, but not prejunctional site (s).