Vasodilation of intramuscular arterioles under shear stress in dystrophin-deficient skeletal muscle is impaired through decreased nNOS expression.
Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder of striated muscle caused by the absence of dystrophin. Recently, impairment of vascular dilation under shear stress has been found in DMD, but the underlying molecular mechanism is not fully understood. Moreover, dilation of intramuscular arterioles, which may be a key to the molecular pathogenesis, has not been addressed yet. We examined dilation of arterioles in the mouse cremaster muscle under shear stress due to ligation. The vasodilation was significantly impaired in dystrophin-deficient mdx mice as well as in neuronal nitric oxide synthase (nNOS)-deficient mice; however, neither endothelial NOS-deficient mice nor alpha1-syntrophin-deficient mice showed any difference in vasodilation from control mice. These results indicate that nNOS is the main supplier of nitric oxide in shear stress-induced vasodilation in skeletal muscle, but that the sarcolemmal localization of nNOS is not indispensable for the function. In contrast, the response to acetylcholine or sodium nitroprusside was not impaired in mdx or nNOS-deficient mice, suggesting that pharmacological treatment using a vasoactive agent may ameliorate skeletal and cardiac muscle symptoms of DMD.
Sato
K
K
Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan.
Yokota
T
T
Ichioka
S
S
Shibata
M
M
Takeda
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D008833:Microcirculation / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000201:enzymology; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism; D013314:Stress, Mechanical; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D009599:Nitroprusside; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D000109:Acetylcholine; D010100:Oxygen; D007213:Indomethacin