Effects of long-term high altitude hypoxemia on [alpha]1-adrenergic receptors in the ovine uterine artery: functional and binding studies. Hu, Xiang-Qun, Lawrence D. Longo, Raymond D. Gilbert, and Lubo Zhang. Center for Perinatal Biology, Departments of Pharmacology, Physiology, and Obstetrics and Gynecology, Loma Linda University School of Medicine, Loma Linda, CA 92350
APStracts 2:0373H, 1995.
To elucidate the effects of chronic hypoxia on [alpha]1-adrenergic receptor-mediated contractions of the uterine artery, we examined norepinephrine-induced contractions in the tissues obtained from near term (140 days gestation) pregnant ewes maintained near sea level (300 m) and at high altitude (3,820 m) from 30 days gestation. Compared with the sea level controls, contractions induced by norepinephrine in both main and fourth branch uterine arteries of the high altitude animals were significantly depressed. The norepinephrine dose-response curves were shifted to the right and EC50s were increased 3.2-fold and 5.7-fold in the main and fourth branch uterine arteries, respectively. The maximal responses were decreased 22% (main) and 36% (fourth branch). The dissociation constants (KA) of norepinephrine were increased from 0.77 to 1.53 [mu]M (main) and from 0.72 to 2.05 [mu]M (fourth branch). Radioligand binding studies with [3H]prazosin revealed a decrease in the density of [alpha]1-adrenergic receptors in both vessels from high altitude animals. We conclude that chronic hypoxia depresses [alpha]1 -adrenergic receptor-induced contractions of both conduit and resistance types of uterine arteries. The depressed contractility is mediated, at least in part, by decreases of [alpha]1-adrenergic receptor density and agonist binding affinity. 

Received 10 April 1995; accepted in final form 21 August 1995.
APS Manuscript Number H348-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 15 September 1995.