title: Role of caveolae in shear stress-mediated endothelium-dependent dilation in coronary arteries.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chai
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Wang
authors.forename: Darryl C
authors.initials: DC
authors.lastname: Zeldin
authors.forename: Hon-Chi
authors.initials: HC
authors.lastname: Lee
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D021941:Caveolae / Q000502:physiology*; D003331:Coronary Vessels / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D004851:Epoxide Hydrolases / Q000502:physiology; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000502:physiology; D013314:Stress, Mechanical; D014664:Vasodilation
chemical_list: D001095:Arachidonic Acids; D052250:Nitric Oxide Synthase Type III; D004851:Epoxide Hydrolases; C518648:Ephx2 protein, mouse; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester
keywords: Calcium; Caveolae; Coronary artery; Shear stress; Soluble epoxide hydrolase