Altered endothelial function in lambs with pulmonary hypertension and acute lung injury. Pediatr Pulmonol 1999 Mar;27(3):147-56
Date
04/23/1999Pubmed ID
10213252DOI
10.1002/(sici)1099-0496(199903)27:3<147::aid-ppul1>3.0.co;2-pScopus ID
2-s2.0-0032945279 (requires institutional sign-in at Scopus site) 23 CitationsAbstract
Acute lung injury produces pulmonary hypertension, altered vascular reactivity, and endothelial injury. To determine whether acute lung injury impairs the endothelium-dependent regulation of pulmonary vascular tone, 16 lambs were studied during U46619-induced pulmonary hypertension without acute lung injury, or air embolization-induced pulmonary hypertension with acute lung injury. The hemodynamic responses to endothelium-dependent (acetylcholine, ATP, ET-1, and 4 Ala ET-1 [an ETb receptor agonist]) and endothelium-independent (nitroprusside and isoproterenol) vasodilators were compared. During U46619-induced pulmonary hypertension, all vasodilators decreased pulmonary arterial pressure and vascular resistance (P < 0.05). During air embolization-induced pulmonary hypertension, the pulmonary vasodilating effects of acetylcholine, ATP, and 4 Ala ET-1 were attenuated (P < 0.05); the pulmonary vasodilating effects of nitroprusside and isoproterenol were unchanged; and the pulmonary vasodilating effects of ET-1 were reversed, producing pulmonary vasoconstriction (P < 0.05). During air embolization, the pulmonary vasoconstricting effects of ET-1 were blocked by BQ 123, an ETa receptor antagonist. The systemic effects of the vasoactive drugs were similar during both conditions. We conclude that pulmonary hypertension with acute lung injury induced by air embolization results in endothelial dysfunction; there is selective impairment of endothelium-dependent pulmonary vasodilation and an altered response to ET-1 from pulmonary vasodilation to vasoconstriction. This altered response to ET-1 is associated with decreased ETb receptor-mediated vasodilation and increased ETa receptor-mediated vasoconstriction. Endothelial injury and dysfunction account, in part, for the altered regulation of pulmonary vascular tone during pulmonary hypertension with acute lung injury.
Author List
Fineman JR, Wong J, Mikhailov T, Vanderford PA, Jerome HE, Soifer SJAuthor
Theresa A. Mikhailov MD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic AcidAcute Disease
Animals
Disease Models, Animal
Embolism, Air
Endothelin-1
Endothelium, Vascular
Hemodynamics
Hypertension, Pulmonary
Lung
Lung Injury
Nitric Oxide
Pulmonary Circulation
Random Allocation
Reference Values
Respiration, Artificial
Sheep
Vascular Resistance
Vasoconstrictor Agents
Vasodilator Agents
