The increased prevalence of obesity in Western society has been well established for many years, and with this trend, the prevalence of other associated pathologies including insulin resistance, dyslipidaemia, hypertension and the genesis of a proinflammatory and prothrombotic environment within individuals is also rapidly increasing, resulting in a condition known as the~metabolic syndrome. From a physiological perspective, one of the most severe consequences of the metabolic syndrome is a progressive inability of the cardiovascular system to adequately perfuse tissues and organs during either elevated metabolic demand and, if sufficiently severe, under basal levels of demand. For the study of the metabolic syndrome, the OZR (obese Zucker rat) represents an important tool in this effort, as the metabolic syndrome in these animals results from a chronic hyperphagia, and thus can be an excellent representation of the human condition. As in afflicted humans, OZR experience an attenuated functional and reactive hyperaemia, and can ultimately experience an ischaemic condition in their skeletal muscles at rest. The source of this progressive ischaemia appears to lie at multiple sites, as endothelium-dependent vasodilator responses are strongly impaired in OZR, and specific constrictor processes (e.g. adrenergic tone) may be enhanced. Whilst these active processes may contribute to a reduction in blood flow under resting conditions or with mild elevations in metabolic demand, an evolving structural alteration to individual microvessels (reduced distensibility) and microvascular networks (reduced microvessel density) also develop and may act to constrain perfusion at higher levels of metabolic demand. Given that constrained muscle perfusion in the metabolic syndrome appears to reflect a highly integrated, multi-faceted effect in OZR, and probably in humans as well, therapeutic interventions must be designed to address each of these contributing elements.
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November 2006
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Review Article|
November 30 2006
Vascular function in the metabolic syndrome and the effects on skeletal muscle perfusion: lessons from the obese Zucker rat
Jefferson C. Frisbee;
Jefferson C. Frisbee
1
*Center for Interdisciplinary Research in Cardiovascular Sciences, West Virginia School of Medicine, Morgantown, WV, U.S.A.
†Department for Physiology and Pharmacology, West Virginia School of Medicine, Morgantown, WV, U.S.A.
1To whom correspondence should be addressed (email [email protected]).
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Michael D. Delp
Michael D. Delp
*Center for Interdisciplinary Research in Cardiovascular Sciences, West Virginia School of Medicine, Morgantown, WV, U.S.A.
‡Division of Exercise Physiology, West Virginia School of Medicine, Morgantown, WV, U.S.A.
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Publisher: Portland Press Ltd
Online ISSN: 1744-1358
Print ISSN: 0071-1365
© 2006 The Biochemical Society, London
2006
Essays Biochem (2006) 42: 145–160.
Citation
Anton J.M. Wagenmakers, Jefferson C. Frisbee, Michael D. Delp; Vascular function in the metabolic syndrome and the effects on skeletal muscle perfusion: lessons from the obese Zucker rat. Essays Biochem 27 November 2006; 42 145–160. doi: https://doi.org/10.1042/bse0420145
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