Endothelin B receptor deficiency potentiates ET-1 and hypoxic pulmonary vasoconstriction

D. Dunbar Ivy, Ivan F. Mcmurtry, Masashi Yanagisawa, Cheryl E. Gariepy, Timothy D. Le Cras, Sarah A. Gebb, Kenneth G. Morris, Richard C. Wiseman, Steven H. Abman

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Endothelin (ET)-1 contributes to the regulation of pulmonary vascular tone by stimulation of the ETA and ETB receptors. Although activation of the ETA receptor causes vasoconstriction, stimulation of the ETB receptors can elicit either vasodilation or vasoconstriction. To examine the physiological role of the ETB receptor in the pulmonary circulation, we studied a genetic rat model of ETB receptor deficiency [transgenic(sl/sl)]. We hypothesized that deficiency of the ETB receptor would predispose the transgenic(sl/sl) rat lung circulation to enhanced pulmonary vasoconstriction. We found that the lungs of transgenic(sl/sl) rats are ETB deficient because they lack ETB mRNA in the pulmonary vasculature, have minimal ETB receptors as determined with an ET-1 radioligand binding assay, and lack ET-1-mediated pulmonary vasodilation. The transgenic(sl/sl) rats have higher basal pulmonary arterial pressure and vasopressor responses to brief hypoxia or ET-1 infusion. Plasma ET-1 levels are elevated and endothelial nitric oxide synthase protein content and nitric oxide production are diminished in the transgenic(sl/sl) rat lung. These findings suggest that the ETB receptor plays a major physiological role in modulating resting pulmonary vascular tone and reactivity to acute hypoxia. We speculate that impaired ETB receptor activity can contribute to the pathogenesis of pulmonary hypertension.

Original languageEnglish (US)
Pages (from-to)L1040-L1048
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume280
Issue number5 25-5
StatePublished - May 1 2001

Keywords

  • Hypoxia
  • Nitric oxide
  • Pulmonary circulation

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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    Ivy, D. D., Mcmurtry, I. F., Yanagisawa, M., Gariepy, C. E., Le Cras, T. D., Gebb, S. A., Morris, K. G., Wiseman, R. C., & Abman, S. H. (2001). Endothelin B receptor deficiency potentiates ET-1 and hypoxic pulmonary vasoconstriction. American Journal of Physiology - Lung Cellular and Molecular Physiology, 280(5 25-5), L1040-L1048.