期刊
CIRCULATION RESEARCH
卷 93, 期 5, 页码 456-463出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.RES.0000090994.15442.42
关键词
hypoxia; vascular permeability; albumin extravasation; HIF-1 alpha
资金
- NHLBI NIH HHS [K08 HL003823-04, HL03823, HL04484] Funding Source: Medline
Endothelin ( ET) may contribute to pulmonary edema formation, particularly under hypoxic conditions, and decreases in ET-B receptor expression can lead to reduced ET clearance. ET increases vascular endothelial cell growth factor ( VEGF) production in vitro, and VEGF overexpression in the lung causes pulmonary edema in vivo. We hypothesized that pulmonary vascular ET-B receptor deficiency leads to increased lung ET, that excess ET increases lung VEGF levels, promoting pulmonary edema formation, and that hypoxia exaggerates these effects. We studied these hypotheses in ET-B receptor-deficient rats. In normoxia, homozygous ET-B-deficient animals had significantly more lung vascular leak than heterozygous or control animals. Hypoxia increased vascular leak regardless of genotype, and hypoxic ET-B-deficient animals leaked more than hypoxic control animals. ET-B-deficient animals had higher lung ET levels in both normoxia and hypoxia. Lung HIF-1alpha and VEGF content was greater in the ET-B-deficient animals in both normoxia and hypoxia, and both HIF-1alpha and VEGF levels were reduced by ET-A receptor antagonism. Both ET-A receptor blockade and VEGF antagonism reduced vascular leak in hypoxic ET-B-deficient animals. We conclude that ET-B receptor-deficient animals display an exaggerated lung vascular protein leak in normoxia, that hypoxia exacerbates that leak, and that this effect is in part attributable to an ET-mediated increase in lung VEGF content.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据