CHARACTERIZATION OF ENDOTHELIN RECEPTORS MEDIATING CONTRACTION AND RELAXATION IN RABBIT SAPHENOUS ARTERY AND VEIN

The endothelin receptors in rabbit isolated rings of saphenous artery and saphenous vein have been characterized using endothelin-1, endothelin-2, endothelin-3, sarafotoxin S6c, and BQ123. Although artery rings were more sensitive than those from vein to the contractile action of phenylephrine, endothelin-1 was about three times more potent as a contractile agonist on vein than on artery. In rings precontracted with phenylephrine, carbachol was 10 times more potent in vein than in artery rings to induce endothelium-dependent relaxation. However, in rings precontracted to a similar tone by endothelin-1, the relaxation elicited by carbachol was reduced in the vein but remained unchanged in the artery. In endothelium-denuded saphenous artery, endothelin-1 and endothelin-2 elicited contraction with equal potency, whereas endothelin-3 and sarafotoxin S6c were weak agonists. In saphenous vein, the rank order of sensitivity was sarafotoxin S6c > endothelin-2 greater than or equal to endothelin-1 = endothelin-3, whereas sarafotoxin S6c and, to a lesser extent, endothelin-3 act as partial agonists. The ET(A) receptor antagonist BQ123 shifted, to the right, the concentration-response curves of endothelin-1 on endothelium-denuded saphenous artery (pA(2) = 7.25). In the endothelium-denuded saphenous vein, 10 mu M BQ123 shifted to the right only the response to high concentrations of endothelin-1. In vein but not in artery, endothelin-1, in the presence of BQ123. These results indicate that the rabbit saphenous vein contains a mixed population of ET(A) and ET(B) vasoconstrictor receptors located in the smooth muscle cells and vasorelaxant ET(B) receptors situated on endothelial cells. In contrast, the saphenous artery only possesses smooth muscle cell ET(A) receptors responsible for constriction.