Endothelin receptor subtypes and their functional relevance in human small coronary arteries

1 The potent constrictor peptide endothelin (ET) has been implicated in various cardiovascular disorders including myocardial infarction and atherosclerosis. We have investigated the nature of ET receptor subtypes present on human small coronary arteries. 2 Small coronary arteries were mounted in a wire-myograph for in vitro pharmacology. To investigate the ET receptor subtypes present in dierent segments of the coronary vascular tree, arteries were grouped according to internal diameter. Responses in arteries with small internal diameters (mean 316.7+7.9 mm; Group B) were compared to those in larger arteries (mean 586.2+23.1 mm; Group A). 3 ET-1 consistently and potently contracted arteries from Group A and B, with EC50 values of 1.7 (0.9 – 3.2) nM (n=15) and 2.3 (1.4 – 4.2) nM (n=14), respectively. No correlation was observed between ET-1 potency and internal diameter. The response to ET-1 was potently antagonized by the selective ETA receptor antagonist PD156707 in both Group A and Group B, yielding pA2 values of 8.60+0.12 (n=4 – 6) and 8.38+0.17 (n=4 – 6), respectively. Slopes from Schild regression were not significantly dierent from unity