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Distinct temporal phases of microvascular rarefaction in skeletal muscle of obese Zucker rats.
Frisbee, Jefferson C; Goodwill, Adam G; Frisbee, Stephanie J; Butcher, Joshua T; Brock, Robert W; Olfert, I Mark; DeVallance, Evan R; Chantler, Paul D.
Afiliación
  • Frisbee JC; Department of Physiology and Pharmacology, West Virginia University Health Sciences Center, Morgantown, West Virginia; Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia jefrisbee@hsc.wvu.edu.
  • Goodwill AG; Department of Physiology and Pharmacology, West Virginia University Health Sciences Center, Morgantown, West Virginia; Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia.
  • Frisbee SJ; Department of Health Policy, Management and Leadership, West Virginia University Health Sciences Center, Morgantown, West Virginia; Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia.
  • Butcher JT; Department of Physiology and Pharmacology, West Virginia University Health Sciences Center, Morgantown, West Virginia; Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia.
  • Brock RW; Department of Physiology and Pharmacology, West Virginia University Health Sciences Center, Morgantown, West Virginia; Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia.
  • Olfert IM; Division of Exercise Physiology, West Virginia University Health Sciences Center, Morgantown, West Virginia; and Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia.
  • DeVallance ER; Division of Exercise Physiology, West Virginia University Health Sciences Center, Morgantown, West Virginia; and Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia.
  • Chantler PD; Division of Exercise Physiology, West Virginia University Health Sciences Center, Morgantown, West Virginia; and Center for Cardiovascular and Respiratory Sciences, West Virginia University Health Sciences Center, Morgantown, West Virginia.
Am J Physiol Heart Circ Physiol ; 307(12): H1714-28, 2014 Dec 15.
Article en En | MEDLINE | ID: mdl-25305181
ABSTRACT
Evolution of metabolic syndrome is associated with a progressive reduction in skeletal muscle microvessel density, known as rarefaction. Although contributing to impairments to mass transport and exchange, the temporal development of rarefaction and the contributing mechanisms that lead to microvessel loss are both unclear and critical areas for investigation. Although previous work suggests that rarefaction severity in obese Zucker rats (OZR) is predicted by the chronic loss of vascular nitric oxide (NO) bioavailability, we have determined that this hides a biphasic development of rarefaction, with both early and late components. Although the total extent of rarefaction was well predicted by the loss in NO bioavailability, the early pulse of rarefaction developed before a loss of NO bioavailability and was associated with altered venular function (increased leukocyte adhesion/rolling), and early elevation in oxidant stress, TNF-α levels, and the vascular production of thromboxane A2 (TxA2). Chronic inhibition of TNF-α blunted the severity of rarefaction and also reduced vascular oxidant stress and TxA2 production. Chronic blockade of the actions of TxA2 also blunted rarefaction, but did not impact oxidant stress or inflammation, suggesting that TxA2 is a downstream outcome of elevated reactive oxygen species and inflammation. If chronic blockade of TxA2 is terminated, microvascular rarefaction in OZR skeletal muscle resumes, but at a reduced rate despite low NO bioavailability. These results suggest that therapeutic interventions against inflammation and TxA2 under conditions where metabolic syndrome severity is moderate or mild may prevent the development of a condition of accelerated microvessel loss with metabolic syndrome.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Músculo Esquelético / Microvasos / Obesidad Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Am J Physiol Heart Circ Physiol Asunto de la revista: CARDIOLOGIA / FISIOLOGIA Año: 2014 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Músculo Esquelético / Microvasos / Obesidad Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Am J Physiol Heart Circ Physiol Asunto de la revista: CARDIOLOGIA / FISIOLOGIA Año: 2014 Tipo del documento: Article
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