Characterization of endothelin receptors in the human umbilical artery and vein

1 The aim of the present study was to characterize pharmacologically endothelin receptors that are present in human umbilical vessels. 2 Endothelin-l (ET-1) and endothelin-2 (ET-2) are potent stimulants of both the human umbilical artery (PEC(50) 7.9 and 7.5) and vein (pEC(50) 8.1 and 8.0). Endothelin-3 (ET-3) is inactive on the artery but contracts the vein (pEC(50) 7.6). IRL1620 is inactive in both vessels. The order of potency of agonists is suggestive of a typical ET(A) receptor in the artery (ET-1=ET-2 much greater than ET-3) and a mixture of ET(A) and ET(B) receptors in the vein (ET-1=ET-2 greater than or equal to ET-3). 3 The selective ET(A) receptor antagonist, BQ123, competitively inhibits the effect of ET-1 in the human umbilical artery (pA(2) 6.9), while in the vein, only a mixture of BQ123 and BQ788 (a selective ET(B) antagonist) weakly displaces to the right the cumulative concentration-response curve to ET-1. Contractions induced by ET-3 in the vein are inhibited by BQ788 (pA(2) 7.6), but not by BQ123. 4 Inhibition of Ca2+ channels by nifedipine (0.1 mu M) is accompanied by a significant decrease of the maximal response to ET-I by 40% in the artery and by 30% in the vein. The response of the vein to ET-3 is almost abolished by nifedipine. 5 The results indicate that: (i) endothelins contract the human isolated umbilical artery via stimulation of an ET(A) receptor type; (ii) the contraction induced by ET-1 in the vein is mediated by both ET(A) and ET(B) receptors, while ET-3 stimulates the ET(B) receptor; (iii) the contribution of Ca2+ channels to the contraction mediated by the ET(B) receptor appears to be more important than to that mediated by the ET(A) receptor.