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1 Vascular Biology Center and Department of Physiology, Medical College of Georgia, Augusta, GA, USA
2 Department of Physiology, Medical College of Wisconsin, Augusta, GA, USA
* To whom correspondence should be addressed. E-mail: dstepp{at}mcg.edu.
Peripheral microvascular dysfunction is a common affliction in patients with the Metabolic Syndrome X. Previous studies have described a number of vascular impairments in vasomotor control in both human patients and animal models of Syndrome X but the net effect of these impairments on microvascular structure has not been examined. The goal of the current study was to test the hypothesis that Syndrome X reduces muscle perfusion and induces vascular remodeling. The Obese Zucker rat was used as a model of Syndrome X and the microcirculation of the hindlimb and brain were examined. Obese Zucker Rats were obese, hyperlipidemic, hyperinsulinemic and hyperglycemic. Blood flow to the hindlimb was reduced by 59% in Obese rats relative to Lean rats. Skeletal muscle resistance arteries of the hindlimb microcirculation of Obese rats had thinner walls, smaller lumens and reduced distensibility. Hindlimb microvessels from Obese rats also demonstrated reduced expression of vascular smooth muscle cells markers. Each of these traits is consistent with low-flow remodeling. In contrast, the cerebral microcirculation, where flow is vigorously autoregulated, showed no vascular remodeling nor were there changes in microvascular smooth muscle marker expression. Neither physical activity nor muscle mass were significantly different between Lean and Obese rats. Taken together, these findings suggest that Syndrome X, by reducing hindlimb blood flow, induces a marked remodeling of microcirculation to favor smaller, less distensible vessels. This remodeling may result in an architectural limitation of maximum perfusion capacity and may be an important maladaption in the progression of peripheral microvascular disease.
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