ATP-gated potassium channel activity of pulmonary resistance vessels in the lamb

There are conflicting reports on the role of ATP-gated potassium channels (K(ATP)) in the perinatal pulmonary circulation. To investigate this issue, we have used isolated pulmonary resistance vessels from near-term fetal lambs and have tested levcromakalim and glybenclamide, respectively a K(ATP) Opener and blocker, on muscle tone at fetal and neonatal Pot, and under hypoxia. Levcromakalim (from 1 mu M upwards) relaxed arteries and veins precontracted with a thromboxane A(2) (TXA(2)) analogue (ONO-11113) at neonatal PO(2). This effect was nearly completely inhibited by glybenclamide (10 mu M) and N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mu M). Conversely, levcromakalim relaxed little arteries precontracted with activating solution (5 mM Ca(2+) in K(+)-Krebs) or hypoxia. Equally modest was the response of endothelium-denuded, ONO-11113-contracted arteries. Glybenclamide (10 mu M) by itself did not raise the basal tone of vessels, regardless of PO(2). We conclude that fetal pulmonary resistance vessels have K(ATP) channels. In the arteries, these channels are located in the endothelium, and their opening causes relaxation by promoting nitric oxide formation. However, this relaxing mechanism does not become active when PO(2) is raised from fetal to neonatal levels, nor does its inhibition contribute to hypoxic vasoconstriction.