ATP-dependent K+ channel activation in isolated normal and hypertensive newborn and adult porcine pulmonary vessels

The role of an ATP-dependent K+ channel (K-ATP)(+) relaxation in the porcine pulmonary vasculature from birth to adulthood was investigated in vitro using levcromakalim on isolated, prostaglandin F-2 alpha (30 mu M)-precontracted conduit arteries (CA), resistance arteries (RA), and veins (PV). Vessels from neonatal pulmonary hypertensive piglets exposed to chronic hypobaric hypoxia (CHH, 51 kPa) for 3 d, either from birth or from 3 d of age were also studied. Levcromakalim relaxed all vessels in a concentration-and glibenclamide-sensitive manner. In normal CA, the maximal extent of relaxation and sensitivity (EC50) increased between birth and 17 d. Endothelium-removal increased EC50 at 17 d only. Indomethacin (10 mu M), but not N-G-monomethyl-L-arginine (L-NMMA) (30 mu M), inhibited relaxation in CA from newborn, 3-d-old, and adult animals. In RA, levcromakalim-induced relaxations did not change during development and endothelium-removal attenuated relaxations in 3-d-old but not in adult animals. At both ages in RA, L-NMMA attenuated relaxations and subsequent addition of L-arginine (1 mM) restored them. In PV, maximal relaxation increased between birth and 6 d with no change of EC50. At all ages, relaxation was partially endothelium-dependent and inhibited by L-NMMA (except in the newborn). Indomethacin only attenuated relaxations in veins from 6- and 17-d-old animals. CHH did not influence relaxant responses in CA and PV but decreased EC50 in RA. Thus K-(ATP)(+) channel activation caused relaxation from birth onward in all vascular segments with varying endothelium dependence. CHH did not affect relaxation in the large Vessels and up-regulated those in RA. These findings indicate a possible role for K-(ATP)(+) channels during normal adaptation and a potential therapeutic role in the management of pulmonary hypertensive newborn infants.