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1 Center for Perinatal Biology, Department of Physiology & Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA
* To whom correspondence should be addressed. E-mail: lzhang{at}som.llu.edu.
Little is known about the adaptation of contractile mechanisms of uterine artery smooth muscle to pregnancy. The present study tested the hypothesis that pregnancy differentially regulates thick and thin filament regulatory pathways in the uterine artery. Isometric tension, intracellular free Ca2+ concentration ([Ca2+]i), and phosphorylation of 20 kDa myosin light chain (MLC20) were measured simultaneously in uterine arteries isolated from nonpregnant and near-term (140 days gestation) pregnant sheep. Phenylephrine-mediated [Ca2+]i, MLC20 phosphorylation and contractions were significantly increased in pregnant, as compared with nonpregnant, uterine arteries. In contrast, phenylephrine-mediated Ca2+ sensitivity of MLC20 phosphorylation was decreased in the pregnant uterine arteries. Simultaneous measurement of phenylephrine-stimulated tension and MLC20 phosphorylation in the same tissue indicated a decrease in MLC20 phosphorylation-independent contractions in the pregnant uterine arteries. In addition, activation of protein kinase C (PKC) produced significantly lower sustained contractions in pregnant, as compared with nonpregnant, uterine arteries in the absence of changes in MLC20 phosphorylation levels in either vessel. In the nonpregnant uterine arteries, the MEK/ERK inhibitor PD098059 significantly increased phenylephrine-mediated, MLC20 phosphorylation-independent contractions. The results suggest that in the uterine artery pregnancy up-regulates
1-adrenoceptor-mediated Ca2+ mobilization and MLC20 phosphorylation. In contrast, pregnancy down-regulates the Ca2+ sensitivity of myofilaments, which is mediated by both thick and thin filament pathways.
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