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

1 The receptors mediating endothelin-evoked contraction of human coron ary artery have been investigated in isolated segments of the left ant erior descending coronary artery (LAD). 2 Endothelin-1 (ET-1) was 10 t imes more potent in distal than in proximal segments but the potency r atio 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 (pA 2 equal to 7.47). In the proximal segments, part of the contractile re sponse was BQ123 sensitive, but the antagonism was non-competitive. In both groups of segments, the response to ET-3 could be completely blo cked by BQ-123. 4 These observations indicate that ET(A) receptors med iate the contractile response to ET-1 in distal, pre-resistant coronar y arteries, but that other ET receptors are also involved in the contr actile response of proximal segments.