Effects of l ‐N G ‐nitro‐arginine on noradrenaline induced contraction in the rat anococcygeus muscle

The influence of l ‐N G ‐nitro‐arginine ( l ‐NOARG, 30 μ m ) on contractile responses to exogenous noradrenaline was studied in the rat anococcygeus muscle. Noradrenaline (0.1–100 μ m ) contracted the muscle in a concentration‐dependent manner. l ‐NOARG (30 μ m ) had no effect on noradrenaline responses. Phenoxybenzamine (Pbz 0.1 μ m ) depressed by 46% ( P <0.001) the maximum response and shifted to the right ( P <0.001) the E/[A] curve to noradrenaline (pEC 50 control: 6.92±0.09; pEC 50 Pbz: 5.30±0.10; n =20). 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. Contractile responses to noradrenaline after partial α 1 ‐adrenoceptor alkylation with phenoxybenzamine (0.1 μ m ) were clearly enhanced by l ‐NOARG. The potentiating effect of l ‐NOARG on noradrenaline responses after phenoxybenzamine was reversed by (100 μ m ) l ‐arginine but not by (100 μ m ) d ‐arginine. These results indicate that spontaneous release of NO by nitrergic nerves can influence the α 1 ‐adrenoceptor‐mediated response to exogenous noradrenaline.British Journal of Pharmacology (1997) 120 , 1035–1038; doi: 10.1038/sj.bjp.0701005