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

The pulmonary vascular resistance decreases at birth secondary to release of endothelium-derived nitric oxide (EDNO). EDNO release is a calcium-dependent process, and endothelial potassium (K+) channels regulate intracellular calcium flux. We investigated the hypothesis that potassium channels mediate oxygen-induced pulmonary vasodilation and EDNO release in fetal lambs. We instrumented 18 near-term fetal lambs at 122-126 days of gestation to measure pulmonary pressures, flow, and resistance. We studied hemodynamic effects of (1) 100% oxygen; (2) pinacidil, an ATP-sensitive K+ (KATP) channel agonist, and (3) S-nitroso-N-acetylpenicillamine (SNAP), a NO donor. We studied the effects of glybenclamide, a K(ATP) channel antagonist, tetraethylammonium chloride (TEA), a preferential KCa channel antagonist, and nitro-L-arginine (NLA), an NO synthase inhibitor, on the response to some of the above agents. Oxygen-induced pulmonary vasodilation was inhibited by both glybenclamide and TEA, indicating that K(ATP) and K(Ca) channels mediate pulmonary vasodilator response to oxygen. Blocking NO synthesis with NLA inhibited pinacidil-mediated pulmonary vasodilation, indicating that K(ATP) channel activation stimulates NO release. SNAP-mediated pulmonary vasodilation was inhibited by TEA, but not glybenclamide, indicating that K(Ca) channels, but not K(ATP) channels, mediate effects of NO on vascular smooth muscle relaxation. In conclusion, K+ channels mediate oxygen-induced pulmonary vasodilation in fetal lambs. K(ATP) channels appear to mediate EDNO release, while K(Ca) channels probably mediate NO effects on vascular smooth muscle.