Characterization of endothelin receptors in the human umbilical artery and vein

Abstract

1The aim of the present study was to characterize pharmacologically endothelin receptors that are present in human umbilical vessels. 2 Endothelin-1 (ET-1) and endothelin-2 (ET-2) are potent stimulants of both the human umbilical artery (pEC5o 7.9 and 7.5) and vein (pEC50 8.1 and 8.0). Endothelin-3 (ET-3) is inactive on the artery but contracts the vein (pEC50 7.6). IRL1620 is inactive in both vessels. The order of potency of agonists is suggestive of a typical ETA receptor in the artery (ET-1 = ET-2 > > ET-3) and a mixture of ETA and ETB receptors in the vein (ET-1 = ET-2> ET-3). 3 The selective ETA receptor antagonist, BQ123, competitively inhibits the effect of ET-1 in the human umbilical artery (pA2 6.9), while in the vein, only a mixture of BQ123 and BQ788 (a selective ETB 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 (pA2 7.6), but not by BQ123.4 Inhibition of Ca21 channels by nifedipine (0.1 ,uM) is accompanied by a significant decrease of the maximal response to ET-1 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 ETA receptor type; (ii) the contraction induced by ET-1 in the vein is mediated by both ETA and ETB receptors, while ET-3 stimulates the ETB receptor; (iii) the contribution of Ca21 channels to the contraction mediated by the ETB receptor appears to be more important than to that mediated by the ETA receptor.

Endothelin B Receptors on Vascular Smooth Muscle Cells of the Human Umbilical Vein Mediate Vasoconstriction

“…Our results are in line with those of Bogoni et al [13] , who found that endothelin-3 induced contraction of endothelium-denuded strip preparations of human umbilical veins. This contraction was inhibited by the selective ETB receptor antagonist BQ-788, but not by the selective ETA receptor antagonist BQ-123.…”

Endothelin-1 and -2: Two amino acids matter

“…When compared in vessels from the same animals, the potency (pD 2 : 8.4 ± 0.1 and 8.5 ± 0.1, respectively) and the maximal effect (E MAX : 102 ± 5% vs. 99 ± 10%) did not differ significantly between both peptides (Fig. 1A), in line with earlier findings (Bogoni et al, 1996;Saito et al, 1991) and in addition their effects were equally persistent ( Fig. 1D and F).…”

Immunohistochemical Localization of Carboxypeptidases E and D in the Human Placenta and Umbilical Cord

“…Furthermore, vascular smooth muscle cells in other tissues produce insulin-like growth factor, insulin growth factor binding proteins 3, 4 and 6, platelet-derived growth factor, fibroblast growth factor (Cohick et al 1993;Arnqvist et al 1995;Delafontaine 1995), transforming growth factor-␤ 1 and 2 and activin A (Kanzaki et al 1995), and transforming growth factor-␤ 3 (Stewart et al 1996). Endothelin-1 is predominantly produced by endothelial cells and then binds to specific receptors on vascular smooth muscle cells, which, in fact, have been identified in the human umbilical artery and vein (Bogoni et al 1996). Smooth muscle cells from human microvessels in culture were also shown to produce ET-1 (Anfossi et al 1993).…”