AJP - Heart and Circulatory Physiology, Vol 270, Issue 3 1001-H1007, Copyright © 1996 by American Physiological Society

ARTICLES

Effects of long-term high-altitude hypoxemia on alpha 1-adrenergic receptors in the ovine uterine artery

X. Q. Hu, L. D. Longo, R. D. Gilbert and L. Zhang
Department of Pharmacology, Loma Linda University School of Medicine, California 92350, USA.

To elucidate the effects of chronic hypoxia on alpha 1-adrenergic receptor-mediated contractions of the uterine artery, we examined norepinephrine-induced contractions in tissues obtained from near-term (approximately 140 days gestation) pregnant ewes maintained near sea level (approximately 300 m) and at high altitude (3,820 m) from 30 days gestation. Compared with the sea-level controls, contractions induced by norepinephrine in 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 the concentrations at which 50% of the maximal response was attained were increased 3.2- and 5.7-fold in the main and fourth-branch uterine arteries, respectively. The maximal responses were decreased 22 and 36% in main and fourth-branch uterine arteries, respectively. The dissociation constants of norepinephrine were increased from 0.77 to 1.53 microM and from 0.72 to 2.05 microM in main and fourth-branch uterine arteries, respectively. 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 conduit- and resistance-type uterine arteries. The depressed contractility is mediated, at least in part, by decreases in alpha 1-adrenergic receptor density and agonist binding affinity.

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