Altered endothelial function in lambs with pulmonary hypertension and acute lung injury

Jeffrey R. Fineman, Jackson Wong, Theresa Mikhailov, Paula Vanderford, Heidi E. Jerome, Scott J. Soifer

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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 ET(b) 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 ET(a) 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 ET(b) receptor-mediated vasodilation and increased ET(a) 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.

Original languageEnglish (US)
Pages (from-to)147-156
Number of pages10
JournalPediatric Pulmonology
Volume27
Issue number3
DOIs
StatePublished - Mar 1999
Externally publishedYes

Fingerprint

Acute Lung Injury
Pulmonary Hypertension
Lung
Endothelium
Vasoconstriction
Air
Vasodilation
Blood Vessels
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Nitroprusside
Vasodilator Agents
Isoproterenol
Acetylcholine
Adenosine Triphosphate
Wounds and Injuries
Vascular Resistance
Arterial Pressure
Hemodynamics

Keywords

  • Acute lung injury
  • Endothelial function
  • Endothelin
  • Lambs
  • Nitric oxide
  • Pulmonary circulation
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pulmonary and Respiratory Medicine

Cite this

Altered endothelial function in lambs with pulmonary hypertension and acute lung injury. / Fineman, Jeffrey R.; Wong, Jackson; Mikhailov, Theresa; Vanderford, Paula; Jerome, Heidi E.; Soifer, Scott J.

In: Pediatric Pulmonology, Vol. 27, No. 3, 03.1999, p. 147-156.

Research output: Contribution to journalArticle

Fineman, Jeffrey R. ; Wong, Jackson ; Mikhailov, Theresa ; Vanderford, Paula ; Jerome, Heidi E. ; Soifer, Scott J. / Altered endothelial function in lambs with pulmonary hypertension and acute lung injury. In: Pediatric Pulmonology. 1999 ; Vol. 27, No. 3. pp. 147-156.
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