Impaired Vasorelaxation in Inbred Mice Is Associated with Alterations in Both Nitric Oxide and Super Oxide PathwaysChen C. · Korshunov V.A. · Massett M.P. · Yan C. · Berk B.C.
Cardiovascular Research Institute, Department of Medicine, University of Rochester, Rochester, N.Y., USA
Recently, we showed that genetic factors determine flow-dependent vascular remodeling. Among five inbred mouse strains, the SJL strain developed the largest intima in response to low flow. Because SJL mice have a spontaneous mutation in superoxide dismutase 2 (SOD-2) we tested the hypothesis that strain-specific variations in vascular function are due to alterations in redox and nitric oxide (NO) pathways. Vasorelaxation to acetylcholine was significantly impaired in aortic rings from SJL compared to C3H or FVB mice (up to 40%). Relaxation to the endothelium-independent vasodilator sodium nitroprusside (SNP) in SJL mice was also significantly impaired at low concentrations, with decreases in sensitivity and maximal relaxation to SNP compared to C3H and FVB mice. Western blot analyses showed significantly decreased expression (∼40%) of eNOS, PKG and SOD-2 proteins in SJL vasculature compared to C3H. Intact aortas from SJL showed significantly increased nitrotyrosine and decreased SOD-2 expression compared to C3H by immunohistochemistry. Basal levels of superoxide in aortas from SJL were not significantly different than C3H as measured by dihydroethidine. In summary, relatively small alterations in redox (SOD-2) and NO pathways (eNOS and PKG) may contribute to significantly impaired vasorelaxation in SJL mice.
© 2007 S. Karger AG, Basel
Received: March 12, 2007
Accepted after revision: May 25, 2007
Published online: July 30, 2007
Number of Print Pages : 9
Number of Figures : 4, Number of Tables : 1, Number of References : 38
Journal of Vascular Research (Incorporating 'International Journal of Microcirculation')
Vol. 44, No. 6, Year 2007 (Cover Date: October 2007)
Journal Editor: Pohl, U. (Munich)
ISSN: 1018–1172 (print), 1423–0135 (Online)
For additional information: http://www.karger.com/JVR