Premium
Effect of N G ‐nitro‐L‐arginine methylester (L‐NAME) on functional and biochemical α 1 ‐adrenoceptor‐mediated responses in rat blood vessels
Author(s) -
Tabernero Antonia,
Giraldo Jesús,
Vila Elisabet
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15255.x
Subject(s) - phenylephrine , aorta , contraction (grammar) , agonist , endocrinology , medicine , phenoxybenzamine , artery , receptor , vasoconstriction , chemistry , anatomy , biology , blood pressure
1 The modulation by N G ‐nitro‐L‐arginine methylester (L‐NAME) of α 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 α 1 ‐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 μ m ) enhanced the sensitivity (3.3 times) and the maximum contraction (E max ) induced by the full agonist, phenylephrine. 3 St‐587, a partial α 1 ‐adrenoceptor agonist, behaved as a weak agonist in the aorta (22.2% of phenylephrine E max ). However, when the same agonist was studied in tail artery rings a maximum contraction that was 78.4% of the phenylephrine induced E max was reached. 4 L‐NAME increased (3.3 times) the E max 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 E max 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 α 1 ‐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 α 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.