Peripheral Circulation M. Harold Laughlin, * 1,2 Michael J. Davis, 2 Niels H. Secher, 3 Johannes J. van Lieshout, 4 Arturo A. Arce-Esquivel, 1 Grant H. Simmons, 1 Shawn B. Bender, 1 Jaume Padilla, 1 Robert J. Bache, 5 Daphne Merkus, 6 and Dirk J. Duncker 6 ABSTRACT Blood flow (BF) increases with increasing exercise intensity in skeletal, respiratory, and cardiac muscle. In humans during maximal exercise intensities, 85% to 90% of total cardiac output is distributed to skeletal and cardiac muscle. During exercise BF increases modestly and hetero- geneously to brain and decreases in gastrointestinal, reproductive, and renal tissues and shows little to no change in skin. If the duration of exercise is sufficient to increase body/core tem- perature, skin BF is also increased in humans. Because blood pressure changes little during exercise, changes in distribution of BF with incremental exercise result from changes in vascular conductance. These changes in distribution of BF throughout the body contribute to decreases in mixed venous oxygen content, serve to supply adequate oxygen to the active skeletal muscles, and support metabolism of other tissues while maintaining homeostasis. This review discusses the response of the peripheral circulation of humans to acute and chronic dynamic exercise and mechanisms responsible for these responses. This is accomplished in the context of leading the reader on a tour through the peripheral circulation during dynamic exercise. During this tour, we consider what is known about how each vascular bed controls BF during exercise and how these control mechanisms are modified by chronic physical activity/exercise training. The tour ends by comparing responses of the systemic circulation to those of the pulmonary circulation relative to the effects of exercise on the regional distribution of BF and mechanisms responsible for control of resistance/conductance in the systemic and pulmonary circulations. C  2012 American Physiological Society. Compr Physiol 2:321-447, 2012. Introduction The transition from rest to dynamic exercise in humans pro- duces amazing adjustments in the cardiovascular system that are the result of large changes in heart rate (HR), blood pres- sure, cardiac output, and the regional distribution of cardiac output (950, 951, 1177). Figure 1 illustrates the impact of in- cremental exercise on key cardiovascular variables: cardiac output, HR, stroke volume, mean arterial pressure (MAP), systemic vascular conductance, and several variables that summarize oxygen delivery to the tissues of the body in normal humans. These changes are coordinated by the sym- pathetic nervous system through an increased sympathetic outflow to the heart (thereby increasing cardiac output) and the peripheral circulation (producing redistribution of cardiac output and overall peripheral vasoconstriction), activated by the reflexes to prevent a decrease in blood pressure. Adjustments in the cardiovascular system are necessary during exercise to coordinate delivery of oxygen and nutri- ents to the tissues, where they are most needed to face the dramatic increases in metabolic requirements in the body. As illustrated in Figure 1, the increased metabolism during exercise is sustained by both increases in oxygen delivery (increased cardiac output, obtained through increases in HR and stroke volume) and increased oxygen carrying capacity of the blood, as well as by increases in oxygen extraction [increased arterio-venous O 2 (a-vO 2 ) difference as shown in the center right column of data in Figure 1]. The dramatic increase in a-vO 2 difference occurs because of redistribution of cardiac output in the systemic circulation and increased oxygen extraction by the tissues. The progressive increases in vascular conductance, related to increasing exercise inten- sity (illustrated in Figure 1, bottom left column of data), may obscure some very interesting and important decreases in vas- cular conductance in the tissues of the human body that cause altered regional distribution of cardiac output. Thus, although the changes in conductance in active muscle and other tissues * Correspondence to laughlinm@missouri.edu 1 Department of Biomedical Sciences 2 Department of Medical Pharmacology and Physiology, and the Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri 3 Department of Anesthesia, Rigshospitalet, Copenhagen Muscle Research Center, University of Copenhagen, Copenhagen, Denmark 4 Department of Internal Medicine and Laboratory for Clinical Cardiovascular Physiology, Academic Medical Center Center for Heart Failure Research, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands 5 Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 6 Experimental Cardiology, Thoraxcenter, Cardiovascular Research Institute COEUR, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands Published online, January 2012 (comprehensivephysiology.com) DOI: 10.1002/cphy.c100048 Copyright C  American Physiological Society Volume 2, January 2012 321