Referenced in: none

Automatically associated channels: Kir6.2

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

Authors: P J Boels, B Gao, J Deutsch, S G Haworth

Journal, date & volume: Pediatr. Res., 1997 Sep , 42, 317-26

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/9284272

Abstract
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 F2alpha (30 microM)-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 microM), but not N(G)-monomethyl-L-arginine (L-NMMA) (30 microM), 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.