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

Abstract

There are conflicting reports on the role of ATP-gated potassium channels (KATP) 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 KATP opener and blocker, on muscle tone at fetal and neonatal PO2, and under hypoxia. Levcromakalim (from 1 microM upwards) relaxed arteries and veins precontracted with a thromboxane A2 (TXA2) analogue (ONO-11113) at neonatal PO2. This effect was nearly completely inhibited by glybenclamide (10 microM) and NG-nitro-L-arginine methyl ester (L-NAME, 100 microM). Conversely, levcromakalim relaxed little arteries precontracted with activating solution (5 mM Ca2+ in K(+)-Krebs) or hypoxia. Equally modest was the response of endothelium-denuded, ONO-11113-contracted arteries. Glybenclamide (10 microM) by itself did not raise the basal tone of vessels, regardless of PO2. We conclude that fetal pulmonary resistance vessels have KATP 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 PO2 is raised from fetal to neonatal levels, nor does its inhibition contribute to hypoxic vasoconstriction.