EVIDENCE FOR HETEROGENEITY OF ENDOTHELIN RECEPTOR DISTRIBUTION IN HUMAN CORONARY-ARTERY

1 The receptors mediating endothelin-evoked contraction of human coronary artery have been investigated in isolated segments of the left anterior descending coronary artery (LAD). 2 Endothelin-1 (ET-1) was 10 times more potent in distal than in proximal segments but the potency ratio between ET-1 and ET-3 (endothelin-3) was similar and close to 100 in any segment of the artery. 3 BQ-123, an ET(A) receptor antagonist, competitively antagonized the response to ET-1 of distal segments (pA2 equal to 7.47). In the proximal segments, part of the contractile response was BQ123 sensitive, but the antagonism was non-competitive. In both groups of segments, the response to ET-3 could be completely blocked by BQ-123. 4 These observations indicate that ET(A) receptors mediate the contractile response to ET-1 in distal, pre-resistant coronary arteries, but that other ET receptors are also involved in the contractile response of proximal segments.