AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 2 201-L206, Copyright © 1995 by American Physiological Society
Inhibition of dihydropyridine-sensitive calcium entry in hypoxic relaxation of airway smooth muscle
C. Vannier, T. L. Croxton, L. S. Farley and C. A. Hirshman
Department of Environmental Health Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Hypoxia dilates airways in vivo and reduces active tension of airway smooth
muscle in vitro. To determine whether hypoxia impairs Ca2+ entry through
voltage-dependent channels (VDC), we tested the ability of dihydropyridines
to modulate hypoxia-induced relaxation of KCl- and carbamyl choline
(carbachol)-contracted porcine bronchi. Carbachol- or KCl-contracted
bronchial rings were exposed to progressive hypoxia in the presence or
absence of 1 microM BAY K 8644 (an L-type-channel agonist). In separate
experiments, rings were contracted with carbachol or KCl, treated with
nifedipine (a VDC antagonist), and finally exposed to hypoxia. BAY K 8644
prevented hypoxia-induced relaxation in KCl-contracted bronchi. Nifedipine
(10(-5) M) totally relaxed KCl- contracted bronchi. Carbachol-contracted
bronchi were only partially relaxed by nifedipine but were completely
relaxed when the O2 concentration of the gas was reduced from 95 to 0%.
These data indicate that hypoxia can reduce airway smooth muscle tone by
limiting entry of Ca2+ through a dihydropyridine-sensitive pathway, but
that other mechanisms also contribute to hypoxia-induced relaxation of
carbachol-contracted bronchi.
