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-l (ET-I) of human placental vasculature. 2 Isolated stem villi small arteries (di ameter = 170-250 mu m) were obtained from healthy parturients who unde rwent 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-I (10(-12) to 10( -6) M). 3 The vasocontractile response to ET-I 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 N-omega- 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 relax ation = 70 +/- 7%) at 10(-9) M, which was followed, at higher doses (1 0(-8) to 10(-6) M), by a contraction. In contrast, no relaxation was s een in endothelial-denuded rings. The relaxation in rings with endothe lium was significantly (P<0.001) reduced by L-NOARG (10(-4) M). Moreov er, it was totally abolished by combined pretreatment with L-NOARG (10 (-4) M) and the sulphonylurea glibenclamide (10(-5) M). 5 In conclusio n, endothelial cells modulate the vascular responses to ET-1 through t he release of NO and a substance acting on the ATP-sensitive K+ channe l of smooth muscle of stem villi small arteries from healthy parturien ts.