title: Diethylamine/nitric oxide (NO) adduct, an NO donor, produces potent pulmonary and systemic vasodilation in intact newborn lambs.
abstract: Nitric oxide (NO), a labile humoral factor produced by vascular endothelial cells, is a potent vasodilator and an important mediator of pulmonary vascular tone. Nucleophile/NO adducts are a new class of compounds that spontaneously and predictively release NO. We investigated the hemodynamic effects of intravenous (i.v.) infusions of a recently developed NO-donor drug, the diethylamine-nitric oxide adduct (DEA/NO), in 17 intact newborn lambs. At rest, DEA/NO (1-2 microgram.kg-1.min-1) produced dose-dependent decreases in mean pulmonary (from 10.6 +/- 8.6 to 21.2 +/- 7.9%, p < 0.05) and systemic arterial pressure (from 13.2 +/- 11.7 to 31.0 +/- 15.4%, p < 0.05). Similarly, during pulmonary hypertension induced by infusion of U46619, DEA/NO (0.5-2.0 micrograms.kg-1.min-1) produced dose-dependent decreases in mean pulmonary (from 7.3 +/- 5.6 to 24.1 +/- 13.3%, p < 0.05) and systemic arterial pressure (from 2.2 +/- 3.8 to 20.3 +/- 12.9%, p < 0.05). Cardiac output (CO), heart rate (HR), systemic arterial blood gases, and pH were unchanged; atrial pressures decreased at higher doses. Equimolar infusions of S-nitroso-N-acetyl-penicillamine, nitroglycerin (NTG), and sodium nitroprusside (SNP) produced similar decreases in pulmonary and systemic arterial pressure. The nucleophile/NO adducts are potent vasodilators; their predictable and quantitative release of NO make them potentially useful research tools. In addition, because these compounds may decrease the incidence of tolerance and the risk from toxic metabolites associated with use of other nitrovasodilators, they may be clinically useful.
authors.affiliation: Department of Pediatrics, University of California San Francisco 94143-0106.
authors.forename: P A
authors.initials: PA
authors.lastname: Vanderford
authors.forename: J
authors.initials: J
authors.lastname: Wong
authors.forename: R
authors.initials: R
authors.lastname: Chang
authors.forename: L K
authors.initials: LK
authors.lastname: Keefer
authors.forename: S J
authors.initials: SJ
authors.lastname: Soifer
authors.forename: J R
authors.initials: JR
authors.lastname: Fineman
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects*; D004048:Diethylamines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy*; D007262:Infusions, Intravenous; D009569:Nitric Oxide / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000633:toxicity; D011651:Pulmonary Artery / Q000187:drug effects*; D012756:Sheep; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000633:toxicity; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000633:toxicity; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D004048:Diethylamines; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009569:Nitric Oxide; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C034281:diethylamine