Kelland N F, Bagnall A J, Morecroft I, Gulliver-Sloan F H, Dempsie Y, Nilsen M, Yanagisawa M, Maclean M R, Kotelevtsev Y V, Webb D J
Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
J Vasc Res. 2010;47(1):16-22. doi: 10.1159/000231717. Epub 2009 Aug 6.
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.
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.
我们推测内皮素B（ET(B)）的潜在保护作用在限制肺血管肌化、血管收缩以及低氧诱导的肺动脉高压发展中具有重要意义。
将内皮细胞特异性ET(B)基因敲除小鼠（EC ET(B)(-/-)）和对照小鼠（ET(B)(f/f)）置于低压低氧（10% FiO2）或常氧条件下14天，然后评估右心室压力以及肺血管形态和功能。
在常氧状态下，EC ET(B)(-/-)小鼠（23.7±1.7 mmHg）和ET(B)(f/f)小鼠（20.2±1.5 mmHg）的右心室压力未检测到差异。低氧诱导EC ET(B)(-/-)小鼠右心室压力过度升高（34.4±1.2 mmHg对24.6±1.4 mmHg），同时伴有右心室质量增加。在ET(B)(f/f)小鼠中未观察到影响。内皮素-1使两组小鼠的肺动脉收缩，尽管无论吸入氧气或基因型如何，最大反应相似。低氧增加了两组小鼠肌化血管的百分比，但EC ET(B)(-/-)小鼠的百分比增加显著更大。
内皮ET(B)的潜在保护作用在限制肺血管肌化和低氧诱导的肺动脉高压发展中具有重要意义。
