Thomas MM, Wang DC, D'Souza DM, Krause MP, Layne AS, Criswell DS, O'Neill HM, Connor MK, Anderson JE, Kemp BE, Steinberg GR, Hawke TJ. Muscle-specific AMPK β1β2-null mice display a myopathy due to loss of capillary density in nonpostural muscles. FASEB J, 2014 May;28(5):2098-107.
While it has been previously shown that nNOSμ is involved in matching blood supply to the metabolic demands of the active muscle, the present findings demonstrate for the first time a critical relationship between AMPK and nNOSμ in resting skeletal muscle. This relationship allows the energy-sensing enzyme of skeletal muscle to readily regulate perfusion in resting non-postural muscles at times of energy need; findings that support a novel model to help explain the heterogeneity of vascular perfusion that is observed in resting skeletal muscle. In the absence of AMPK, an impaired vasodilatory capacity and increased platelet aggregation ensues, resulting in functional ischemia and downstream apoptosis. The outcome is significant muscle pathology, including a loss of capillary content and exercise intolerance.
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