Thus, the sarcolemmal localization of nNOS through expression of α1-syntrophin is not indispensable for vasodilation. However, how dystrophin or other molecules transduce mechanostress to soluble nNOS is unresolved (6). The defective vasodilation under shear stress due to nNOS deficiency in mdx mice might be related to its selleck chemicals llc muscle degradation (14). It is very interesting to note the amelioration of dystrophic phenotypes in nNOS transgenic mdx mice, although

the localization Inhibitors,research,lifescience,medical of nNOS cannot have been improved (30). Decreased vasodilation just after muscle contraction has also been demonstrated in mdx skeletal muscle (31). Leinonen et al. found that capillary circulation in skeletal muscle was impaired in DMD (32), and deteriorated attenuation of α-adrenergic vasoconstriction

Inhibitors,research,lifescience,medical during exercise may participate in this pathophysiology (7). Moreover, blood flow must be increased to accommodate the augmented metabolic demands of the muscle, not only in exercise. Intramuscular arterioles in mdx mice cannot afford to respond to the increased demands, Inhibitors,research,lifescience,medical and their failure may result in relative ischemia in the skeletal muscle and cardiac phenotypes of dystrophin deficiency. Asai et al. very recently showed that the functional ischemia in contraction-induced myofibers in mdx mice is due to nNOS deficiency and indicated that vasoactive drugs may ameliorate muscle damage (33). Even in dystrophin-deficient skeletal muscle, cholinergic vascular modulation was well preserved. Therefore, our study indicates that pharmacological Inhibitors,research,lifescience,medical treatment using a

vasoactive agent is applicable to at least skeletal muscle symptoms in patients suffering from DMD. In conclusion, we demonstrated that vasodilation of intramuscular arterioles under shear stress was impaired in dystrophin-deficient mdx mice. This impairment may be related to phenotypes of DMD, not only in skeletal muscle but also in cardiac muscle. Acknowledgments This work was supported by Grants-in-Aid from the Human Frontier Science Program, Scientific Research for Center Inhibitors,research,lifescience,medical of Excellence, Research on Nervous and Mental Disorders (10B-1, 13B-1), Health Science Research Grants for Research on the Human Genome and Gene Therapy (H10-genome-015, H13-genome-001) and for Research on Brain Science (H12-brain-028) from the Ministry of Health, Labor, and Welfare of Japan, Grants-in-Aid for Scientific Research (10557065, Bumetanide 11470153, 11170264, 14657158, and 15390281) from the Ministry of Education, Culture, Sports, Science, and Technology for Japan, and a Research Grant from the Human Frontier Science Project. This work was also carried out as a part of the “Ground-based Research Announcement for Space Utilization” promoted by the Japan Space Forum. T. Yokota is a Research Fellow of the Japan Society for the Promotion of Science (JSPS).