Vascular potassium channels mediate oxygen-induced pulmonary vasodilation in fetal lambs

The pulmonary vascular resistance decreases at birth secondary to release o f endothelium-derived nitric oxide (EDNO). EDNO release is a calcium-depend ent process, and endothelial potassium (K+) channels regulate intracellular calcium flux. We investigated the hypothesis that potassium channels media te oxygen-induced pulmonary vasodilation and EDNO release in fetal lambs. W e instrumented 18 near-term fetal lambs at 122-126 days of gestation to mea sure pulmonary pressures, flow, and resistance. We studied hemodynamic effe cts of (1) 100% oxygen; (2) pinacidil, an ATP-sensitive K+ (K-ATP) channel agonist, and (3) S-nitroso-N-acetylpenicillamine (SNAP), a NO donor. We stu died the effects of glybenclamide, a K-ATP channel antagonist, tetraethylam monium chloride (TEA), a preferential K-Ca channel antagonist, and nitro-L- arginine (NLA), an NO synthase inhibitor, on the response to some of the ab ove agents. Oxygen-induced pulmonary vasodilation was inhibited by both gly benclamide and TEA, indicating that K-ATP and K-Ca channels mediate pulmona ry vasodilator response to oxygen. Blocking NO synthesis with NLA inhibited pinacidil-mediated pulmonary vasodilation, indicating that K-ATP channel a ctivation stimulates NO release. SNAP-mediated pulmonary vasodilation was i nhibited by TEA, but not glybenclamide, indicating that K-Ca channels, but not K-ATP channels, mediate effects of NO on vascular smooth muscle relaxat ion. in conclusion, K+ channels mediate oxygen-induced pulmonary vasodilati on in fetal lambs. K-ATP channels appear to mediate EDNO release, white K-C a channels probably mediate NO effects on vascular smooth muscle. Copyright (C) 2000 S. Karger AG, Basel.