Diethylamine/nitric oxide (no) adduct, an no donor, produces potent pulmonary and systemic vasodilation in intact newborn lambs

Paula A. Vanderford, Jackson Wong, Roger Chang, Larry K. Keefer, Scott J. Soifer, Jeffrey R. Fineman

Research output: Contribution to journalArticle

34 Scopus citations

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 H-g 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 μg 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-acetylpenicillamine, nitroglycerin (NTG), and sodium nitro-prusside (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 nitrova-sodilators, they may be clinically useful.

Original languageEnglish (US)
Pages (from-to)113-119
Number of pages7
JournalJournal of Cardiovascular Pharmacology
Volume23
Issue number1
DOIs
StatePublished - Jan 1994

Keywords

  • Nitric oxide donors
  • Nitrovasodilators
  • Nucleophile/nitric oxide adducts
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Diethylamine/nitric oxide (no) adduct, an no donor, produces potent pulmonary and systemic vasodilation in intact newborn lambs'. Together they form a unique fingerprint.

  • Cite this