INHIBITION OF DIHYDROPYRIDINE-SENSITIVE CALCIUM-ENTRY IN HYPOXIC RELAXATION OF AIRWAY SMOOTH-MUSCLE

Hypoxia dilates airways in vivo and reduces active tension of airway s mooth muscle in vitro. To determine whether hypoxia impairs Ca2+ entry through voltage-dependent channels (VDC), we tested the ability of di hydropyridines to modulate hypoxia-induced relaxation of KCl- and carb amyl choline (carbachol)-contracted porcine bronchi. Carbachol- or KCl -contracted bronchial rings were exposed to progressive hypoxia in the presence or absence of 1 mu M 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 hy poxia. BAY K 8644 prevented hypoxia-induced relaxation in KCl-contract ed bronchi. Nifedipine (10(-5) M) totally relaxed KCl-contracted bronc hi. Carbachol-contracted bronchi were only partially relaxed by nifedi pine but were completely relaxed when the O-2 concentration of the gas was reduced from 95 to 0%. These data indicate that hypoxia can reduc e airway smooth muscle tone by limiting entry of Ca2+ through a dihydr opyridine-sensitive pathway, but that other mechanisms also contribute to hypoxia-induced relaxation of carbachol-contracted bronchi.