Endothelial modulation of vasoconstrictor responses to endothelin‐1 in human placental stem villi small arteries

1 The aim of this study was to assess the role of endothelial cells in the modulation of vasocontractile responses to endothelin‐1 (ET‐1) of human placental vasculature. 2 Isolated stem villi small arteries (diameter =170–250 μ m ) were obtained from healthy parturients who underwent caesarean surgery during the 39th week of pregnancy for cephalo‐pelvic disproportion. Isometric tension was measured in vascular rings mounted in a myograph system and challenged with ET‐1 (10 −12 to 10 −6 m ). 3 The vasocontractile response to ET‐1 was significantly ( P < 0.0001) increased in endothelial‐denuded (active tension = 1156 ±214 mN mm −1 ) as compared with endothelial‐preserved vascular rings (active tension = 458 ± 48 mN mm −1 ). This difference was significantly (P<0.05) but only partly abolished by the NO synthase inhibitor NΩ‐nitro‐L‐arginine (l‐NOARG, 10 −4 m). 4 In endothelial‐preserved rings submaximally precontracted with 5‐hydroxytryptamine (10 −6 m), ET‐1 (10 −12 to 10 −9 m) induced dose‐dependent relaxation (maximum relaxation = 70 ±7%) at 10 −9 m , which was followed, at higher doses (10 −8 to 10 −6 m ), by a contraction. In contrast, no relaxation was seen in endothelial‐denuded rings. The relaxation in rings with endothelium was significantly ( P < 0.001) reduced by l‐NOARG (10 −4 m). Moreover, it was totally abolished by combined pretreatment with L‐NOARG (10 −4 m) and the sulphonylurea glibenclamide (10 −5 m). 5 In conclusion, endothelial cells modulate the vascular responses to ET‐1 through the release of NO and a substance acting on the ATP‐sensitive K + channel of smooth muscle of stem villi small arteries from healthy parturients.