Microvascular Dysfunction A Potential Pathophysiological Role in the Metabolic Syndrome

TL;DR: The present article examines recent data concerning the role of microvascular dysfunction as an explanation for the associations among hypertension, obesity, and impaired insulin-mediated glucose disposal with a focus on the microcirculation.

Abstract: Obesity and a central body fat distribution, hypertension, insulin resistance, glucose intolerance, dyslipidemia, and proinflammatory and prothrombotic factors are all part of the metabolic syndrome. The metabolic syndrome defines a clustering of metabolic risk factors which confers an increased risk for type 2 diabetes and cardiovascular disease.1 In the past years a large amount of research has been aimed at elucidating the pathophysiology underlying this clustering of risk factors, because a better understanding may lead to new therapeutic approaches that specifically target underlying causes of the metabolic syndrome. Recently, it has become clear that microvascular dysfunction, by affecting both pressure and flow patterns, may have consequences not only for peripheral vascular resistance, but also for insulin-mediated changes in muscle perfusion and glucose metabolism, providing a novel pathophysiological framework for understanding the association between hypertension, obesity, and impaired insulin-mediated glucose disposal.2–4 The present article examines recent data concerning the role of microvascular dysfunction as an explanation for the associations among hypertension, obesity, and impaired insulin-mediated glucose disposal. Description of the Microcirculation An exact definition of the microcirculation is elusive. Morphologically, the microcirculation is widely taken to encompass vessels 150 m in diameter. It therefore includes arterioles, capillaries, and venules. Alternatively, a definition based on arterial vessel physiology rather than diameter or structure has been proposed. 3 By this definition, all arterial vessels that respond to increasing pressure by a myogenic reduction in lumen diameter are included in the microcirculation. Such a definition would include the smallest arteries and arterioles in the microcirculation in addition to capillaries and venules. Small arterial and arteriolar components should, therefore, be considered a continuum rather than distinct sites of resistance control. A primary function of the microcirculation is to optimize nutrient and oxygen supply within the tissue in response to variations in demand. A second important function is to avoid large fluctuations in hydrostatic pressure at the level of the capillaries causing disturbances in capillary exchange. Finally, it is at the level of the microcirculation that a substantial proportion of the drop in hydrostatic pressure occurs. The microcirculation is therefore extremely important in determining overall peripheral vascular resistance.