Contractile Responses to Endothelins in Isolated Arteries from Human Uterus

Choi, Ook Hwan; Jang, Mi Kyung; Rhim, Byung Yong

Abstract

OBJECTIVE
We examined the vasoconstricting poperties of endothelin (ET) on isolated arteries from pregnant as well as non-pregnant uterus.
METHODS
Arteries of the uterus were obtained from both hysterectomized uterus and during pregnany hysterectomy for control group and cesarean section for pregnant group. Rings of uterine artery were suspended on muscle chambers at their optimal length for generating tension and contractile properties were examined.
RESULTS
ET-1 and ET-2 induced concentration-dependent constriction of both isolated arterial strips from non-pregnant and pregnant uterus. The contraction to ET-1 and ET-2 were more enhanced in full-term pregnancy. Furthermore, in pregnant group, sarafotoxin S6c and IRL 1620, ET. agonists, induced a dose-dependent contraction, which was not shown in those from non-pregnant human. Pretreatment of human uterine arterial strips from pregnant uterus with BQ610, an ET. antagonist, for 10 min resulted in a dose-related rightward shift of ET-1 response curve with diminution of maximal response. Schild plot analysis yielded a pA value of 7.29 with a slope of 0.98. However, BQ788, an ET antagonist, did not produce any rightward shift. The contraction to lower concentration (10-8~3*10-7 M) of sarafotoxin S6c was not affected by BQ788, whereas that to higher concentration (10-s-8*10-7 M) was marked diminished. However, BQ610 did not exnt any efFect on sarafotoxin S6c-induced contraction in arterial staips from pregnant uterus. When the bath solution was replaced with Ca-free physiological salt solution (PSS) containing 1 mM EGTA for 10 min prior to adding sarafotoxin S6c, sarafotoxin S6c-induced contraction was completely abolished. Sarafotoxin S6c (10 nM)-induced contraction was prefetentially blocked by a protein kinase C antagonist, H-7, whereas it was less sensitive to a calmodulin antagonist, calmidazolium,
CONCLUSION
Based on above results, we concluded that ET plays an important role in regulating uterine blood flow through the activation of ETa and ETB receptors. Furthermote, ETB receptors may predominantly contribute to the modulation of human uterine circulation in full-term pregnancy.