Reduced microvascular flow-mediated dilation in Syrian hamsters lacking δ-sarcoglycan is caused by increased oxidative stress.

δ-Sarcoglycan mutation reduces mechanotransduction and induces dilated cardiomyopathy with aging. We hypothesized that in young hamsters with δ-sarcoglycan mutation, which do not show cardiomyopathy, flow mechanotransduction might be affected in resistance arteries as the control of local blood flow. Flow-mediated dilation (FMD) was measured in isolated mesenteric resistance arteries, using 3-mo-old hamsters carrying a mutation in the δ-sarcoglycan gene (CH-147) and their control littermates. The FMD was significantly reduced in the CHF-147 group. Nevertheless, passive arterial diameter, vascular structure, and endothelium-independent dilation to sodium nitroprusside were not modified. Contraction induced by KCl was not modified, whereas contraction due to phenylephrine was increased. The basal nitric oxide production and total endothelial nitric oxide synthase (eNOS) expression levels were not altered. Nevertheless, eNOS phosphorylation, focal adhesion kinases, and RhoA expression were reduced in CH-147. In contrast, p47phox, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase, and reactive oxygen species (ROS) levels were higher in the endothelium of CHF-147 hamsters. Reducing ROS levels using the superoxide dismutase analog Tempol significantly restored the flow-mediated dilation (FMD) levels in CHF-147 hamsters. However, treatment with the COX-2 inhibitor NS-398 showed a nonsignificant improvement in FMD.NEW & NOTEWORTHY This study suggests that the sarcoglycan complex is selectively involved in flow-mediated dilation, thus highlighting its role in endothelial responsiveness to shear stress and amplifying tissue damage in myopathy.