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BOR - Papers in Press, published online ahead of print December 17, 2003.
Biol Reprod 2003, 10.1095/biolreprod.103.024943
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Submitted October 30, 2003
Returned for revision December 7, 2003
Accepted December 9, 2003

Pregnancy


Calcium Homeostasis and Contraction of the Uterine Artery: Effect of Pregnancy and Chronic Hypoxia

DaLiao Xiao and Lubo Zhang *

* To whom correspondence should be addressed. E-mail: lzhang{at}som.llu.edu.

Abstract
The present study tested the hypothesis that chronic hypoxia alters pregnancy-mediated adaptation of Ca2+ homeostasis and contractility in the uterine artery. Uterine arteries were isolated from nonpregnant and near-term pregnant ewes of normoxic control or high altitude (3,820 m) hypoxic (PaO2: 60 mmHg) treatment for 110 days. Contractions and intracellular free Ca2+ concentration ([Ca2+]i) were measured simultaneously in the same tissue. In normoxic animals, pregnancy increased norepinephrine (NE), but not 5-HT or KCl, contractile sensitivity in the uterine artery. Chronic hypoxia significantly attenuated NE-induced contractions in the pregnant, but not nonpregnant, uterine arteries. Similarly, 5-HT-mediated contractions of nonpregnant arteries were not changed. In the pregnant uterine artery, chronic hypoxia significantly increased NE-mediated Ca2+ mobilization, but decreased the Ca2+ sensitivity. In addition, hypoxia increased the calcium ionophore A23187-induced relaxation in pregnant, but not nonpregnant, uterine arteries. However, the A23187-mediated reduction of [Ca2+]i was significantly impaired in hypoxic arteries. In contrast, hypoxia significantly increased the slope of the [Ca2+]i-tension relationship of A23187-induced reductions in [Ca2+]i and tension in the pregnant uterine artery. The results suggest that the contractility of nonpregnant uterine artery is insensitive to moderate chronic hypoxia, but the adaptation of sympathetic tone that normally occurs in the uterine artery during pregnancy is inhibited by chronic hypoxia. In addition, changes in Ca2+ sensitivity of myofilaments play a predominant role in the adaptation of uterine artery contractility to pregnancy and chronic hypoxia.

Key words: Environment • Pregnancy • Calcium • Catecholamines • Nitric oxide


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