Mediators of alkalosis-induced relaxation in pulmonary arteries from normoxic and chronically hypoxic piglets

Alkalosis-induced relaxation was measured in precontracted arterial rings f rom 1-wk-old piglets exposed to normoxia or to 3 days of chronic hypoxia. I n normoxic piglet arteries, alkalosis-induced relaxation was blunted in art eries without functional endothelium and in arteries treated with nitric ox ide synthase or guanylate cyclase inhibitors but not in arteries treated wi th cyclooxygenase inhibitors or Ca2+- and ATP-dependent K+-channel inhibito rs. Inhibition of voltage-dependent K+ channels with 10(-3) M 4-aminopyridi ne also failed to block alkalosis-induced relaxation. 4-Aminopyridine at 10 (-2) M did block the response, but this may have been due to sustained vasc ular smooth muscle depolarization. Arteries from hypoxic piglets exhibited greater contraction to the thromboxane mimetic U-46619, decreased endotheli um-dependent relaxation, and blunted alkalosis-induced relaxation. The resi dual relaxation was eliminated by nitric oxide synthase but not by cyclooxy genase or voltage-dependent K+-channel inhibition. Alkalosis-induced relaxa tion of newborn piglet pulmonary arteries appears to be mediated by the nit ric oxide-cGMP pathway and is attenuated after 3 days of hypoxia, likely be cause of decreased nitric oxide activity.