TY - JOUR
T1 - Diethylamine/nitric oxide (no) adduct, an no donor, produces potent pulmonary and systemic vasodilation in intact newborn lambs
AU - Vanderford, Paula A.
AU - Wong, Jackson
AU - Chang, Roger
AU - Keefer, Larry K.
AU - Soifer, Scott J.
AU - Fineman, Jeffrey R.
PY - 1994/1
Y1 - 1994/1
N2 - 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.
AB - 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.
KW - Nitric oxide donors
KW - Nitrovasodilators
KW - Nucleophile/nitric oxide adducts
KW - Pulmonary hypertension
UR - http://www.scopus.com/inward/record.url?scp=0028055218&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028055218&partnerID=8YFLogxK
U2 - 10.1097/00005344-199401000-00016
DO - 10.1097/00005344-199401000-00016
M3 - Article
C2 - 7511722
AN - SCOPUS:0028055218
SN - 0160-2446
VL - 23
SP - 113
EP - 119
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
IS - 1
ER -