The Human Microcirculation: Regulation of Flow and Beyond

David D Gutterman, Dawid S Chabowski, Andrew O Kadlec, Matthew J Durand, Julie K Freed, Karima Ait-Aissa, Andreas M Beyer, David D Gutterman, Dawid S Chabowski, Andrew O Kadlec, Matthew J Durand, Julie K Freed, Karima Ait-Aissa, Andreas M Beyer

Abstract

The microcirculation is responsible for orchestrating adjustments in vascular tone to match local tissue perfusion with oxygen demand. Beyond this metabolic dilation, the microvasculature plays a critical role in modulating vascular tone by endothelial release of an unusually diverse family of compounds including nitric oxide, other reactive oxygen species, and arachidonic acid metabolites. Animal models have provided excellent insight into mechanisms of vasoregulation in health and disease. However, there are unique aspects of the human microcirculation that serve as the focus of this review. The concept is put forth that vasculoparenchymal communication is multimodal, with vascular release of nitric oxide eliciting dilation and preserving normal parenchymal function by inhibiting inflammation and proliferation. Likewise, in disease or stress, endothelial release of reactive oxygen species mediates both dilation and parenchymal inflammation leading to cellular dysfunction, thrombosis, and fibrosis. Some pathways responsible for this stress-induced shift in mediator of vasodilation are proposed. This paradigm may help explain why microvascular dysfunction is such a powerful predictor of cardiovascular events and help identify new approaches to treatment and prevention.

Keywords: microcirculation; muscle, smooth, vascular; nitric oxide; oxidative stress; vasodilation.

© 2016 American Heart Association, Inc.

Figures

Figure 1
Figure 1
In a healthy heart (left), arteriolar endothelium produces NO, prostacyclin, and/or epoxyeicosatrienoic acids as well as low levels of hydrogen peroxide, which support a quiescent non-proliferative state. With onset of disease, flow through the microvasculature releases hydrogen peroxide, creating a pro-inflammatory environment throughout the organ, potentially leading to hypertrophy, fibrosis, and atherosclerosis.
Figure 2
Figure 2
Proposed mechanism for the stress-induced switch in the mediator of flow-induced dilation. In arterioles from healthy subjects, shear activates production of NO to stimulate dilation and vascular homeostasis (left side of diagram). Vascular stress or presence of coronary disease stimulates pathological basal levels of oxidants and initiates a switch in the mediator of flow-induced dilation from NO to hydrogen peroxide. This switch requires ceramide and a reduction in telomerase. Dilation is maintained but at the expense of vascular inflammation and its consequences.

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