Effect of NG-nitro-L-arginine methylester (L-NAME) on functional and biochemical α1-adrenoceptor-mediated responses in rat blood vessels

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Abstract
1 The modulation by NG-nitro-L-arginine methylester (L-NAME) of α1-adrenoceptor-mediated contraction was investigated on isolated segments of rat tail artery and aorta. The influence of L-NAME on inositol phosphates accumulation by α1-adrenoceptor agonists was also investigated to elucidate the intracellular mechanisms responsible for this modulation. 2 In aorta but not in tail artery L-NAME (30 μm) enhanced the sensitivity (3.3 times) and the maximum contraction (Emax) induced by the full agonist, phenylephrine. 3 St-587, a partial α1-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 (Pmax 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 α1-adrenoceptor agonist. 7 The maximum contraction induced by phenylephrine, after partial α-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 α1-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.