Published online before print November 14, 2002, doi: 10.1161/01.RES.0000047505.11002.81
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Submitted on March 6, 2002
Revised on October 23, 2002
Accepted on November 6, 2002
Defect in Microvascular Adaptation to Chronic Changes in Blood Flow in Mice Lacking the Gene Encoding for Dystrophin
Laurent Loufrani ;
From Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 541 (L.L., D.H.), IFR Circulation-Paris-Nord, Paris VII University, and the Department of Physiology (B.I.L.), AP-HP-Hôpital Lariboisière, Paris, France.
* To whom correspondence should be addressed. E-mail: daniel.henrion{at}larib.inserm.fr.
Dystrophin has a key role in striated muscle mechanotransduction. In mice lacking the gene encoding for dystrophin (mdx mice), the absence of dystrophin and several other proteins of the dystrophin-glycoprotein complex induces a defect in flow (shear stress)-mediated NO-dependent dilation (FMD). Because the endothelium is essential for the adaptation of arteries to chronic changes in blood flow, the long-term consequences of this vascular deficiency might affect flow-induced vascular remodeling. Thus, we submitted mouse mesenteric resistance arteries to chronic changes in flow by alternatively ligating arteries. Arteries were thus submitted to high flow (HF), low flow (LF), or normal flow. After 2 weeks, arteries were studied in vitro in an arteriograph. Increases in diameter (from 174±10 to 210±15 µm, pressure 75 mm Hg) found in HF arteries were not significant in mdx mice. Arterial diameters in LF arteries decreased similarly in control and mdx mice. FMD increased in HF arteries and decreased in LF arteries. FMD was not increased in HF arteries in mdx mice. NO-dependent FMD and NO synthase expression increased in the HF arteries of control mice but not in those of mdx mice. Dilatory and contractile tone, depending on the smooth muscle, was unaffected in HF arteries but decreased in LF arteries of both strains. We conclude that resistance arteries of mdx mice do not adapt properly to chronic changes in flow, inasmuch as the increases in diameter, endothelial NO synthase expression, and FMD did not occur in mdx mice submitted to HF for 2 weeks. This study suggests that blood flow regulation might be disturbed in dystrophin-related myopathies, possibly increasing organ damage.
Key words: microcirculation • cytoskeleton • Duchenne muscular dystrophy • dystrophin • endothelium
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