Flow (Shear Stress)–Induced Endothelium-Dependent Dilation Is Altered in Mice Lacking the Gene Encoding for Dystrophin

Abstract

Background-Dystrophin has a key role in striated muscle mechanotransduction of physical forces. Although cytoskeletal elements play a major role in the mechanotransduction of pressure and flow in vascular cells, the role of dystrophin in vascular function has not yet been investigated. Thus, we studied endothelial and muscular responses of arteries isolated from mice lacking dystrophin (mdx mice). Methods and Results-Carotid and mesenteric resistance arteries 120 m in diameter were isolated and mounted in vitro in an arteriograph to control intraluminal pressure and flow. Blood pressure was not affected by the absence of dystrophin. Pressure-induced (myogenic), phenylephrine-induced, and KCl-induced forms of tone were unchanged. Flow (shear stress)-induced dilation in arteries isolated from mdx mice was decreased by 50% to 60%, whereas dilation to acetylcholine or sodium nitroprusside was unaffected. NG-nitro-L-arginine methyl ester-sensitive flow dilation was also decreased in arteries from mdx mice. Thus, the absence of dystrophin was associated with a defect in signal transduction of shear stress. Dystrophin was present in vascular endothelial and smooth muscle cells, as shown by immunolocalization, and localized at the level of the plasma membrane, as seen by confocal microscopy of perfused isolated arteries. Conclusions-This

Deletion of MLCK210 induces subtle changes in vascular reactivity but does not affect cardiac function

“…Because CO, measured by echocardiography, was similar in both strains, it is likely that overall systemic resistances are not increased in KO mice. These results strengthen the hypothesis that, even though flow-dilation has a key role in the control of local blood flow, it is not necessarily and/or directly related to the basal level of systemic blood pressure (12,18).…”

“…Pressure was then set at 75 mmHg (at which no significant difference in myogenic tone has been observed between groups), and dilation in response to flow was performed. At the end of each experiment, to determine the passive diameter of the artery and to evaluate myogenic tone, arteries were perfused and superfused with a Ca 2ϩ -free PSS containing EGTA (2 mmol/l) and sodium nitroprusside (10 mmol/l) and, pressure steps were repeated (18).…”

Dystrophin-deficient cardiomyopathy in mouse: Expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heart

“…An inappropriate response of nitric oxide could affect vascular resistance and blood pressure. [24], [25] Other significant functional assessments include wall stress, an estimate of how much stress the cardiac muscle fibers are experiencing during systole. This value was significantly increased in mdx mice and indicates that the thinning, poorly functioning myocardium is actually under more stress than the normal heart, possibly contributing to increased myocardial cell death over time.…”

Involvement of angiotensin II in the remodeling induced by a chronic decrease in blood flow in rat mesenteric resistance arteries

“…We also tested the role of superoxide anions and ERK1/2 in inward remodeling, as these molecules are involved in angiotensin II-mediated contraction in mesenteric RAs 18 as well as in cell migration. 19 We used a model previously described in rats 20,21 and mice, 22,23 which allows comparison of RAs submitted to low blood flow to adjacent arteries with normal flow (NF) in the same physiological conditions in vivo, without changes in hemodynamic conditions or hormonal environment.…”