Effects of L-N(G)-nitro-arginine on noradrenaline induced contraction in the rat anococcygeus muscle

1. The influence of L-N(G)-nitro-arginine (L-NOARG, 30 μM) on contractile responses to exogenous noradrenaline was studied in the rat anococcygeus muscle. 2. Noradrenaline (0.1-100 μM) contracted the muscle in a concentration-dependent manner. L-NOARG (30 μM) had no effect on noradrenaline responses. 3. Phenoxybenzamine (Pbz 0.1 μM) depressed by 46% (P < 0.001) the maximum response and shifted to the right (P < 0.001) the E/[A] curve to noradrenaline (pEC50 control: 6.92 ± 0.09; pEC50 Pbz: 5.30 ± 0.10; n = 20). 4. The nested hyperbolic null method of analysing noradrenaline responses after phenoxybenzamine showed that only 0.61% of the receptors need to be occupied to elicit 50% of the maximum response, indicating a very high functional receptor reserve. 5. Contractile responses to noradrenaline after partial α1-adrenoceptor alkylation with phenoxybenzamine (0.1 μM) were clearly enhanced by L-NOARG. 6. The potentiating effect of L-NOARG on noradrenaline responses after phenoxybenzamine was reversed by (100 μM) L-arginine but not by (100 μM) D-arginine. 7. These results indicate that spontaneous release of NO by nitrergic nerves can influence the α1-adrenoceptor-mediated response to exogenous noradrenaline.