Noradrenergic‐nitrergic interactions in the rat anococcygeus muscle: evidence for postjunctional modulation by nitric oxide

1 The distribution of NADPH‐diaphorase positive and catecholamine‐containing nerve structures, and functional noradrenergic‐nitrergic interactions, were studied in the rat anococcygeus muscle. 2 The morphological findings demonstrated NADPH‐diaphorase positive neurones mostly as aggregates in intramural ganglia, nerve tracts and few single nerve fibres forming plexus‐like structures. 3 The nitric oxide synthase inhibitor N G ‐nitro‐ l ‐arginine ( l ‐NOARG) inhibited concentration‐dependently the nitrergic relaxation, an effect reversed by l ‐arginine. The drug had dual effects on noradrenergic contractile responses: at lower concentrations (0.1–10 μ m ) it decreased the amplitude of contractions and this was not affected by l ‐arginine; higher concentrations (50–500 μ m ) potentiated the contractions, an effect that was prevented by l ‐arginine. 4 The electron acceptor, nitro blue tetrazolium (NBT) produced a rapid inhibition of the noradrenergic contractile responses (EC 50 0.178 ± 0.041 μ m ). The drug decreased the tone of the preparations. However, it potentiated concentration‐dependently the nitrergic relaxations. 5 NBT (1 μ m ) had no significant effect on the relaxations induced by exogenously applied nitric oxide (NO)‐donor sodium nitroprusside (SNP, 0.01–50 μ m ). However, the effect of NBT (0.1–10 μ m ) on the electrically induced relaxation was significantly decreased by l ‐NOARG (10 and 50 μ m ). The inhibition was of a non‐competitive type. 6 Neither l ‐NOARG (100 μ m ) nor NBT (1 μ m ) had any effect on the spontaneous or electrically‐induced release of 3 H‐radioactivity from the tissues preincubated in [ 3 H]‐noradrenaline. 7 It is concluded that l ‐arginine‐NO pathway can modulate noradrenergic transmission in the rat anococcygeus muscle at postjunctional, but not prejunctional site(s).