Effects of L-NG-nitro-arginine on noradrenaline induced contraction in the rat anococcygeus muscle.
1. The influence of L-NG-nitro-arginine (L-NOARG, 30 microM) on contractile responses to exogenous noradrenaline was studied in the rat anococcygeus muscle. 2. Noradrenaline (0.1-100 microM) contracted the muscle in a concentration-dependent manner. L-NOARG (30 microM) had no effect on noradrenaline responses. 3. Phenoxybenzamine (Phz 0.1 microM) 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 alpha 1-adrenoceptor alkylation with phenoxybenzamine (0.1 microM) were clearly enhanced by L-NOARG. 6. The potentiating effect of L-NOARG on noradrenaline responses after phenoxybenzamine was reversed by (100 microM) L-arginine but not by (100 microM) D-arginine. 7. These results indicate that spontaneous release of NO by nitrergic nerves can influence the alpha -adrenoceptor-mediated response to exogenous noradrenaline.
Hoyo
Y
Y
Departament of Farmacologia i Terapèutica, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Giraldo
J
J
Vila
E
E
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D010643:Phenoxybenzamine; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D009638:Norepinephrine