Key result
Endothelial ET(B) knockout increases hypoxic RV pressure by ~40% vs controls.
Why the study?
The potential protective effects of endothelial ET(B) in limiting pulmonary vascular muscularisation and pulmonary arterial hypertension development during hypoxia were hypothesised but not established.
Does endothelial ETB deficiency exacerbate hypoxia-induced pulmonary hypertension and vascular remodeling in mice?
Does endothelial ETB deficiency exacerbate hypoxia-induced pulmonary hypertension and vascular remodeling in mice?
Absolute Event Rate: 34.4% vs 24.6%
Endothelial ETB receptors play a protective role in limiting pulmonary vascular remodeling and the development of pulmonary arterial hypertension in response to hypoxia.
Endothelial ET(B) protects against hypoxia-induced PAH in mice; leaves open its therapeutic relevance in human disease.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The potential protective effects of endothelial ET(B) are important in limiting pulmonary vascular muscularisation and the development of pulmonary arterial hypertension in response to hypoxia.
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Kelland et al. (2009) studied Pulmonary hypertension. EC-specific ET(B) knockout vs. ET(B)(f/f) control mice was evaluated on Right ventricular pressure during hypoxia. EC-specific ET(B) knockout mice exhibited an exaggerated increase in right ventricular pressure compared to controls during hypoxia (34.4 +/- 1.2 vs 24.6 +/- 1.4 mm Hg).
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