title: Oxygen-induced pulmonary vasodilation is mediated by adenosine triphosphate in newborn lambs.
abstract: In the fetal lamb, oxygen-induced pulmonary vasodilation is attenuated by the combined use of purinergic receptor P1 and P2y antagonists, which block the effect of adenosine and adenosine triphosphate (ATP), respectively, and by N(omega)-nitro-L-arginine [an inhibitor of endothelium-derived nitric oxide (EDNO) synthesis]. In the newborn lamb, oxygen-induced pulmonary vasodilation is not blocked by N(omega)-nitro-L-arginine. We investigated the role of ATP and adenosine in oxygen-induced pulmonary vasodilation in eight newborn lambs with pulmonary hypertension induced by the thromboxane mimic, U46619. The hemodynamic effects of hyperoxia, ATP, adenosine, sodium nitroprusside (SNP), and acetylcholine (ACh) were compared before and after purinergic receptor blockade with Cibacron blue (CB, a P2y-receptor antagonist) and 8-phenyltheophylline (8PT, a P1-receptor antagonist) individually, together, and on a separate day, after infusion of N(omega)-nitro-L-arginine. During pulmonary hypertension, combined pretreatment with 8PT and CB attenuated the decrease in pulmonary arterial pressure caused by hyperoxia (11.3 vs. 35.2%), ATP (10.6 vs. 32.2%), and adenosine (1.9 vs. 33.7%) without change in the effect of ACh or SNP (p < 0.05). N(omega)-Nitro-L-arginine attenuated the pulmonary vasodilation caused by ATP and ACh but not by hyperoxia, adenosine, or SNP. In the newborn lamb, the pulmonary vasodilating effect of both oxygen and ATP are attenuated by combined P1 and P2y purinergic-receptor antagonists. Postnatally, oxygen-induced pulmonary vasodilation appears to be mediated by ATP through purinergic receptors.
authors.affiliation: Department of Pediatrics, University of New Mexico, Albuquerque, 87131,U.S.A.
authors.forename: M R
authors.initials: MR
authors.lastname: Crowley
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000241:Adenosine / Q000502:physiology; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019335:Nitroarginine / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000633:toxicity; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D058914:Purinergic Antagonists; D012756:Sheep; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000633:toxicity; D014227:Triazines / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000633:toxicity; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; D058914:Purinergic Antagonists; D014227:Triazines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D013928:Thromboxane A2; C012842:Cibacron Blue F 3GA; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; D010100:Oxygen