Endothelial ET(B) Limits Vascular Remodelling and Development of Pulmonary Hypertension during Hypoxia

N F Kelland, A J Bagnall, I Morecroft, F H Gulliver-Sloan, Y Dempsie, M Nilsen, M Yanagisawa, M R Maclean, Y V Kotelevtsev, D J Webb

Research output: Contribution to journalArticlepeer-review

Abstract

Background
We hypothesised that the potential protective effects of endothelial ETB are important in limiting pulmonary vascular muscularisation, vasoconstriction and the development of pulmonary arterial hypertension in response to hypoxia.

Methods
EC-specific ETB knockout mice (EC ETB–/–) and control mice (ETBf/f) were subjected to hypobaric hypoxic (10% FiO2) or normoxic conditions for 14 days before assessment of right ventricular pressure and pulmonary vascular morphology and function.

Results
During normoxia, no difference in right ventricular pressure was detected between EC ETB–/– (23.7 ± 1.7 mm Hg) and ETBf/f mice (20.2 ± 1.5 mm Hg). Hypoxia induced an exaggerated increase in right ventricular pressure in EC ETB–/– mice (34.4 ± 1.2 mm Hg vs. 24.6 ± 1.4 mm Hg), accompanied by an increase in right ventricular mass. No effect was observed in ETBf/f mice. Endothelin-1 constricted pulmonary arteries from both groups, although maximum response was similar irrespective of inspired oxygen or genotype. Hypoxia increased the percentage of muscularised vessels in both groups of mice, but the percentage increase was significantly greater in EC ETB–/– mice.

Conclusions
The potential protective effects of endothelial ETB are important in limiting pulmonary vascular muscularisation and the development of pulmonary arterial hypertension in response to hypoxia.

Original languageEnglish
Pages (from-to)16-22
Number of pages7
JournalJournal of vascular research
Volume47
Issue number1
DOIs
Publication statusPublished - 1 Dec 2009

Keywords / Materials (for Non-textual outputs)

  • ET(B) receptor
  • knockout
  • endothelin
  • pulmonary hypertension

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