INVOLVEMENT OF L-TYPE CALCIUM CHANNELS IN HYPOXIC RELAXATION OF VASCULAR SMOOTH-MUSCLE

In the systemic vasculature, hypoxia elicits a local vasodilator respo nse that may be partially mediated by ionic channels on vascular smoot h muscle, such as adenosine triphosphate sensitive K+ channels. Recent electrophysiological studies suggest that hypoxia may also inhibit vo ltage-dependent Ca2+ channels (L-type) on peripheral vascular smooth m uscle cells. We hypothesized that hypoxia elicits relaxation of vascul ar smooth muscle by inhibiting L-type Ca2+ channels. In endothelium-de nuded rat thoracic aortic rings contracted with phenylephrine, mild an d moderate hypoxia (PO2 35 and 20 mm Hg, respectively) elicited signif icant relaxation. Pretreatment with the L-type Ca2+ channel antagonist nifedipine completely inhibited mild hypoxic relaxation and diminishe d relaxation under moderate hypoxia, whereas glibenclamide, a blocker of adenosine triphosphate sensitive potassium channels, only attenuate d the response to moderate hypoxia. In rings contracted with the L-typ e Ca2+ channel agonist (-)BAY K 8644 both mild and moderate hypoxia el icited almost complete relaxation. Furthermore, in rings contracted wi th hyperkalemic solutions (85 mM K+ or 120 mM K), mild and moderate hy poxia elicited significant relaxations. Thus, we conclude that hypoxia acts directly on vascular smooth muscle to cause relaxation in part b y inhibiting L-type Ca2+ channels.