title: ATP-dependent K+ channel activation in isolated normal and hypertensive newborn and adult porcine pulmonary vessels.
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.
authors.affiliation: Institute of Child Health, Division of Physiology and Pharmacology, London, United Kingdom.
authors.forename: P J
authors.initials: PJ
authors.lastname: Boels
authors.forename: B
authors.initials: B
authors.lastname: Gao
authors.forename: J
authors.initials: J
authors.lastname: Deutsch
authors.forename: S G
authors.initials: SG
authors.lastname: Haworth
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D000959:Antihypertensive Agents / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000601:surgery; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011453:Prostaglandins / Q000494:pharmacology; D011651:Pulmonary Artery / Q000503:physiopathology*; D011667:Pulmonary Veins / Q000503:physiopathology*; D012680:Sensitivity and Specificity; D013552:Swine / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011453:Prostaglandins; D019806:Cromakalim; D019323:omega-N-Methylarginine; D000255:Adenosine Triphosphate; D005905:Glyburide; D007213:Indomethacin