Endothelial ET(B) limits vascular remodelling and development of pulmonary hypertension during hypoxia

NF Kelland, AJ Bagnall, Ian Morecroft, FH Gulliver-Sloan, Yvonne Dempsie, Margaret Nilsen, M Yanagisawa, Margaret R MacLean, YV Kotelevtsev, David J Webb

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19 Citations (Scopus)


We hypothesised that the potential protective effects of endothelial ET(B) are important in limiting pulmonary vascular muscularisation, vasoconstriction and the development of pulmonary arterial hypertension in response to hypoxia.
EC-specific ET(B) knockout mice (EC ET(B)(-/-)) and control mice (ET(B)(f/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. During normoxia, no difference in right ventricular pressure was detected between EC ET(B)(-/-) (23.7 +/- 1.7 mm Hg) and ET(B)(f/f) mice (20.2 +/- 1.5 mm Hg). Hypoxia induced an exaggerated increase in right ventricular pressure in EC ET(B)(-/-) 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 ET(B)(f/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 ET(B)(-/-) mice.
Original languageEnglish
Pages (from-to)16-22
Number of pages7
JournalJournal of Vascular Research
Issue number1
Publication statusPublished - Dec 2009


  • pulmonary arterial hypertension
  • hypoxia
  • right ventricular failure


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