Michelini LC, O'Leary DS, Raven PB, Nobrega AC. Neural control of circulation and exercise: a translational approach disclosing interactions between central command, arterial baroreflex, and muscle metaboreflex*. Am J Physiol Heart Circ Physiol 309: H381-H392, 2015. First published May 29, 2015; doi:10.1152/ajpheart.00077.2015.-The last 100 years witnessed a rapid and progressive development of the body of knowledge concerning the neural control of the cardiovascular system in health and disease. The understanding of the complexity and the relevance of the neuroregulatory system continues to evolve and as a result raises new questions. The purpose of this review is to articulate results from studies involving experimental models in animals as well as in humans concerning the interaction between the neural mechanisms mediating the hemodynamic responses during exercise. The review describes the arterial baroreflex, the pivotal mechanism controlling mean arterial blood pressure and its fluctuations along with the two main activation mechanisms to exercise: central command (parallel activation of central somatomotor and autonomic descending pathways) and the muscle metaboreflex, the metabolic component of exercise pressor reflex (feedback from ergoreceptors within contracting skeletal muscles). In addition, the role of the cardiopulmonary baroreceptors in modulating the resetting of arterial baroreflex is identified, and the mechanisms in the central nervous system involved with the resetting of baroreflex function during dynamic exercise are also described. Approaching a very relevant clinical condition, the review also presents the concept that the impaired arterial baroreflex function is an integral component of the metaboreflex-mediated exaggerated sympathetic tone in subjects with heart failure. This increased sympathetic activity has a major role in causing the depressed ventricular function observed during submaximal dynamic exercise in these patients. The potential contribution of a metaboreflex arising from respiratory muscles is also considered. autonomic; baroreflex; central command; exercise; metaboreflex THIS ARTICLE is part of a collection on 1st Pan American Congress of Physiological Sciences: Physiology Without Borders. Other articles appearing in this collection, as well as a full archive of all collections, can be found online at http://ajpheart.physiology.org/.A wide range of complex but routine behaviors such as feeding, shivering, locomotion, aggressive/defensive, and sexual behaviors triggers concomitant activation of somatomotor and autonomic outflows (47). Dynamic exercise is a complex physiological challenge involving highly coordinated activity of skeletal muscles, rapid and immediate increases in respiratory function, heart rate (HR), stroke volume and cardiac output associated with changes in regional vascular resistance, and redistribution of systemic blood flow that cause a slight increase in mean blood pressure (108). The increased blood flow to active muscles provides the necessary o...