The anatomy and physiology of the microcirculation in human skin are complex. Normal cutaneous microcirculation is organized in two parallel plexuses with capillary loops extending perpendicularly from the superficial plexus. The physiological regulation of cutaneous microcirculation includes specific sympathetic activation, which causes vasoconstriction through the release of norepinephrine, neuropeptide Y, and ATP. A sympathetic cholinergic system is mainly involved in vasodilation through the co-transmission of acetylcholine, vasoactive intestinal peptide, and pituitary adenylate cyclase-activating peptide. Sensory nerves play a major role through the release of calcitonin gene-related peptide and substance P. Endothelium-dependent vasomotion implicates nitric oxide, prostacyclin, endothelium-dependent hyperpolarizing factors, and endothelin. Myogenic response also plays a role and explains why autoregulation is weak but exists in glabrous human skin. Variations in skin blood flow result from highly complex interactions between these mechanisms. In this article, we will detail the anatomy, physiology, and current methods of exploring the human microcirculation. We will further discuss the part played by cutaneous microvascular impairment in the pathophysiology of cardiovascular and metabolic diseases, or diseases more specifically affecting the skin. © 2020 American Physiological Society. Compr Physiol 10:1105-1154, 2020.
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