期刊
CARDIOVASCULAR RESEARCH
卷 100, 期 1, 页码 151-159出版社
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvt157
关键词
Caveolae; Shear stress; Coronary artery; Soluble epoxide hydrolase; Calcium
资金
- National Institute of Health, National Institute of Heart Lung and Blood Institute [HL080118, HL74180]
- Intramural Research program of the National Institute of Environmental Health Sciences [Z01 ES025034]
Caveolae are membrane microdomains where important signalling pathways are assembled and molecular effects transduced. In this study, we hypothesized that shear stress-mediated vasodilation (SSD) of mouse small coronary arteries (MCA) is caveolae-dependent. MCA (80150 m) isolated from wild-type (WT) and caveolin-1 null (Cav-1(/)) mice were subjected to physiological levels of shear stress (125 dynes/cm(2)) with and without pre-incubation of inhibitors of nitric oxide synthase (L-NAME), cyclooxygenase (indomethacin, INDO), or cytochrome P450 epoxygenase (SKF 525A). SSD was endothelium-dependent in WT and Cav-1(/) coronaries but that in Cav-1(/) was significantly diminished compared with WT. Pre-incubation with L-NAME, INDO, or SKF 525A significantly reduced SSD in WT but not in Cav-1(/) mice. Vessels from the soluble epoxide hydrolase null (Ephx2(/)) mice showed enhanced SSD, which was further augmented by the presence of arachidonic acid. In donordetector-coupled vessel experiments, Cav-1(/) donor vessels produced diminished dilation in WT endothelium-denuded detector vessels compared with WT donor vessels. Shear stress elicited a robust intracellular Ca-2 increase in vascular endothelial cells isolated from WT but not those from Cav-1(/) mice. Integrity of caveolae is critical for endothelium-dependent SSD in MCA. Cav-1(/) endothelium is deficient in shear stress-mediated generation of vasodilators including NO, prostaglandins, and epoxyeicosatrienoic acids. Caveolae plays a critical role in endothelial signal transduction from shear stress to vasodilator production and release.
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