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Am J Physiol Heart Circ Physiol 291: H2483-H2492, 2006. First published June 23, 2006; doi:10.1152/ajpheart.00566.2006
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Exercise training blunts microvascular rarefaction in the metabolic syndrome

Jefferson C. Frisbee,1 Julie Balch Samora,1 Jonathan Peterson,2 and Randall Bryner2

1Center for Interdisciplinary Research in Cardiovascular Sciences, 2Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia

Submitted 1 June 2006 ; accepted in final form 21 June 2006

Reduced skeletal muscle microvessel density (MVD) in the obese Zucker rat (OZR) model of the metabolic syndrome is a function of a chronic reduction in vascular nitric oxide (NO) bioavailability. Previous studies suggest that exercise can improve NO bioavailability and reduce chronic inflammation and that low vascular NO bioavailability may be associated with impaired angiogenic responses via increased matrix metalloproteinase (MMP)-2 and MMP-9 activity. As such, we hypothesized that chronic exercise (EX) would increase NO bioavailability in OZR and blunt microvascular rarefaction through reduced MMP activity, and potentially via altered plasma cytokine levels. Ten weeks of treadmill exercise (1 h/day, 5 days/wk, 22 m/min) reduced body mass and fasting insulin and triglyceride levels in EX-OZR vs. sedentary (SED) OZR. In EX-OZR, gastrocnemius muscle MVD was improved by 19 ± 4%, whereas skeletal muscle arteriolar dilation and conduit arterial methacholine-induced NO release were increased. In EX-OZR, functional hyperemia was improved vs. SED-OZR, and minimum vascular resistance within perfused gastrocnemius muscle was reduced, although no change in arteriolar stiffness was identified. Western blotting and gelatin zymography demonstrated that neither expression nor activity of MMP-2 or MMP-9 was altered in skeletal muscle of EX vs. SED animals. Plasma markers of inflammation associated with angiogenesis, monocyte chemoattractant protein-1 and IL-1beta, were increased in SED-OZR and were reduced with training, whereas IL-13 was reduced in SED-OZR and increased with exercise. These data suggest that exercise-induced improvements in skeletal muscle MVD in OZR are associated with increased NO bioavailability and may stem from altered inflammatory profiles rather than MMP function.

skeletal muscle microcirculation; regulation of skeletal muscle perfusion; microvessel density; vascular remodeling; vascular resistance



Address for reprint requests and other correspondence: J. C. Frisbee, Center for Interdisciplinary Research in Cardiovascular Science, Dept. of Physiology and Pharmacology, Robert C. Byrd Health Sciences Center, P.O. Box 9105, West Virginia Univ. School of Medicine, Morgantown, WV 26505 (e-mail: jfrisbee{at}hsc.wvu.edu)




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