Effect of NG-nitro-L-arginine methylester (L-NAME) on functional and biochemical alpha 1-adrenoceptor-mediated responses in rat blood vessels.
1. The modulation by NG-nitro-L-arginine methylester (L-NAME) of alpha 1-adrenoceptor-mediated contraction was investigated on isolated segments of rat tail artery and aorta. The influence of L-NAME on inositol phosphates accumulation by alpha 1-adrenoceptor agonists was also investigated to elucidate the intracellular mechanism responsible for this modulation. 2. In aorta but not in tail artery L-NAME (30 microM) enhanced the sensitivity (3.3 times) and the maximum contraction (Emax) induced by the full agonist, phenylephrine. 3. St-587, a partial alpha 1-adrenoceptor agonist, behaved as a weak agonist in the aorta (22.2% of phenylephrine Emax). However, when the same agonist was studied in tail artery rings a maximum contraction that was 78.4% of the phenylephrine induced Emax was reached. 4. L-NAME increased (3.3 times) the Emax for St-587 contraction in the aorta but not in the tail artery. Sensitivity to St-587 was slightly but significantly (P < 0.001) enhanced (1.9 times) by L-NAME in tail artery segments. 5. Contractile responses to phenylephrine after partial alkylation with phenoxybenzamine were analyzed by the nested hyperbolic null method. To elicit 50% of Emax for contraction only 1.1% of the receptors in the tail artery and 21% of the receptors in the aorta need to be occupied. These results indicate a higher receptor reserve for the tail artery than the aorta. 6. In the tail artery but not in the aorta, St-587 activates phosphoinositide turnover. The presence of L-NAME was without effect on inositol phosphates accumulation induced by this partial alpha 1-adrenoceptor agonist. 7. The maximum contraction induced by phenylephrine, after partial alpha-adrenoceptor alkylation, was enhanced by L-NAME in tail artery rings. However, the NO synthase inhibitor was unable to modify the phenylephrine-induced accumulation of inositol phosphates in the presence of phenoxybenzamine. 8. These results indicate that the differences in St-587-induced contraction and the modulation by L-NAME of alpha 1-adrenoceptor-mediated contraction observed between the tail artery and aorta are associated with differences in receptor reserve. In addition, our biochemical studies indicate that the potentiating effect of L-NAME is independent of intracellular calcium release via phosphatidylinositol turnover.
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Department de Farmacologia i Psiquiatria, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Giraldo
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J
Vila
E
E
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010643:Phenoxybenzamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D013623:Tail / Q000098:blood supply; D014661:Vasoconstriction / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D018340:Receptors, Adrenergic, alpha-1; D010643:Phenoxybenzamine; C030655:St 587; D010656:Phenylephrine; D001120:Arginine; D019001:Nitric Oxide Synthase; D003000:Clonidine; D019331:NG-Nitroarginine Methyl Ester