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Br J Pharmacol. May 1995; 115(1): 191–197.
PMCID: PMC1908752

ETA receptor-mediated constrictor responses to endothelin peptides in human blood vessels in vitro.

Abstract

1. We have characterized the constrictor endothelin receptors present in human isolated blood vessels using ETA and ETB selective agonists and antagonists. 2. Monophasic dose-response curves were obtained for ET-1 with EC50 values of 6.8 nM in coronary artery, 3.9 nM in internal mammary artery, 17.4 nM in pulmonary artery, 14.5 nM in aorta and 3.2 nM in saphenous vein. In coronary artery, ET-2 was equipotent with ET-1 with an EC50 value of 5.7 nM. The non-selective peptide, sarafotoxin 6b, was 2-3 times less potent than ET-1 but the maximum responses to these two were comparable. 3. In each vessel ET-3 was much less active than ET-1. No response was obtained to ET-3 in aorta and pulmonary artery or in up to 50% of coronary artery, mammary artery and saphenous vein preparations. In those preparations that did respond, dose-response curves were incomplete at 300 nM. Variable contractions were also obtained with the ETB-selective agonist, sarafotoxin 6c (S6c). Where responses were detected, although S6c was more potent than ET-1 (EC50 values of 0.6-1.2 nM), the maximum response produced was always less than 20% of that to ET-1. 4. The synthetic ETB agonists, BQ3020 and [1,3,11,15Ala]-ET-1, were without effect in any of the five blood vessels at concentrations up to 3 microM. 5. ET-1-induced vasoconstriction was blocked by the ETA-selective antagonists, BQ123 and FR139317.(ABSTRACT TRUNCATED AT 250 WORDS)

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