Effects of .BETA.-estradiol on vasoconstriction in human umbilical artery and vein

Abstract

Objective To determine the effects of β-estradiol on vasoconstriction in human umbilical artery and vein and its potential mechanisms. Methods Human umbilical cord samples were obtained from 96 term neonates of healthy singleton pregnant women born in the First Hospital of Soochow University between December 2013 and June 2015 (multiple pregnancy, pregnancy complications, cesarean delivery and low birth weight were excluded). Human umbilical arteries and veins were isolated and suspended in 37 ℃ organ baths containing 5 ml Krebs solution and exposed to β-estradiol followed by phenylephrine (PE) for vasoconstriction test. The subjects were divided into β-estradiol group and control group according to the presence or absence of β-estradiol incubation. To determine the effects and the possible underlying mechanisms of β-estradiol on PE-induced vasoconstriction, human umbilical artery and vein rings were pretreated with Nω-nitro-L-arginine (L-NMMA, nitric oxide synthesis inhibitor), fulvestrant (ICI182780, estradiol receptor antagonist), indomethacin (prostaglandin synthesis blocker), and removal of endothelium, then incubated with β-estradiol for 60 min followed by PE, and the concentration-response curves to PE were recorded. The concentration-response curves to phorbol 12,13-dibutyrate (PDBU, protein kinase C agonist) in Krebs solution in the presence or absence of β-estradiol were also obtained. Nonlinear regression and fitting curve were performed, and the two-sample ANOVA was used for analysis. Results (1) β-estradiol suppressed PE-induced vasoconstriction of human umbilical vein and artery. In human umbilical vein and artery of the control group, the maximum contraction intensity induced by PE was (59.17±5.98)% and (43.35±5.02)% of that induced by potassium chloride, respectively. The maximum contraction induced by PE in β-estradiol group was (5.87±1.32)% and (4.52±1.22)% of that induced by potassium chloride. (2) In both groups, incubation with L-NMMA or endothelium removal enhanced the vasoconstriction of human umbilical artery and vein, indicating that the inhibitory effect of β-estradiol was not influenced by the endothelium. (3) The suppression of β-estradiol on PE-induced vasoconstriction in human umbilical artery and vein was not significantly decreased by estrogen receptor antagonist. (4) β-estradiol did not affect human umbilical artery and vein vasoconstriction induced by PDBU. (5) In the control group, incubation with indomethacin did not affect human umbilical artery and vein vasoconstriction induced by PE. In the β-estradiol group, indomethacin significantly enhanced the contraction response induced by PE, suggesting that prostacycline synthesis was partly involved in β-estradiol-suppressed contractility in human umbilical artery and vein. The contractile response induced by phenylephrine was still lower in the β-estradiol group than in the control group, which was induced by indomethacin. Conclusions (1)β-estradiol can suppress vasoconstriction in human umbilical artery and vein, which is not dependent on endothelium and estrogen receptors, or protein kinase C activity. (2) Prostacycline synthesis is partly involved in β-estradiol-suppressed vasoconstriction in human umbilical artery and vein. Key words: Umbilical arteries; Umbilical veins; Vasoconstriction; Estradiol