AIMS: 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.
METHODS AND RESULTS: MCA (80-150 μm) isolated from wild-type (WT) and caveolin-1 
null (Cav-1(-/-)) mice were subjected to physiological levels of shear stress 
(1-25 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 donor-detector-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.
CONCLUSION: 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.