Abstract

Cardiac output and arterial blood pressure increase during dynamic exercise notwithstanding the exercise-induced vasodilation due to functional sympatholysis. These cardiovascular adjustments are regulated in part by neural reflexes which operate to guarantee adequate oxygen supply and by-products washout of the exercising muscles. Moreover, they maintain adequate perfusion of the vital organs and prevent excessive increments in blood pressure. In this review, we briefly summarize neural reflexes operating during dynamic exercise with particular emphasis on their interaction. Hemodynamic Regulation during Dynamic Exercise: General Review and Functions Physical activities with large muscle mass, such as running, cycling, and rowing, can produce a reduction in systemic vascular resistance (SVR) because of the intense metabolic vasodilatation in the muscle vasculature via functional sympatholysis There are at least three neural mechanisms participating in this cardiovascular regulation: (1) the exercise pressor reflex, (2) the central command, and (3) the arterial baroreflex. The medulla contains the major nuclei that control blood pressure and the cardiovascular system. These nervous circuits are extensively reviewed in other excellent papers Thus, dynamic exercise elicits marked cardiovascular and autonomic adjustments which include increases in CO, MAP, and SVR reduction. This hemodynamic status is regulated by the nervous system by the integration of information coming from the motor cortex (central command), from muscle receptors (exercise pressor reflex), and from receptors in the aortic, carotid, heart, and pulmonary arteries (arterial and cardiopulmonary baroreflexes). One key point of the functioning of these reflexes is how they interact during dynamic exercise. There is some redundancy between them and neural occlusion can be operative. Moreover, from several observations it appears that both the central command and the exercise pressor reflex can modulate the activity of the baroreflex Exercise Pressor Reflex Since the seminal research by Alam and Smirk [20, It is well established that these two reflexes have their afferent arm in groups III and IV nerve endings within the muscle, with type III nerve afferents mainly acting as mechanoreceptors and type IV as metaboreceptors Several substances have been demonstrated to be able to activate the metaboreflex, such as lactic acid, potassium, bradykinin, arachidonic acid products, ATP, deprotonated phosphate, and adenosine From a hemodynamic point of view, the typical consequence of metaboreflex recruitment is an increase in MAP In healthy individuals, the metaboreflex can also influence cardiac contractility, preload, and stroke volume (SV) as suggested by recent and past evidence BioMed Research International 3 Thus, the available literature suggests that the hemodynamic response to metaboreflex activation is a highly integrated phenomenon. A complex interplay between HR, cardiac performance, preload, and afterload occurs to achieve, at least in healthy individuals, the normal cardiovascular response to exercise As concerns the mechanical branch of the exercise pressor reflex, it has been reported that the mechanoreflex can also trigger cardiovascular reflex. Actually, mechanical distortion of type III nerve endings in contracting muscles may substantially increase blood pressure In summary, from available data it seems that the exercise pressor reflex can adjust all four hemodynamic modulators (i.e., chronotropism, inotropism, cardiac preload, and afterload) to reach the target blood pressure during exercise. However, while the metaboreflex contribution to this reflex is well characterized, less is known about the hemodynamic effects of mechanoreflex activation. Central Command The Nobel Prize winning Krogh and his colleague Lindhard It has been demonstrated that central command consists of neural impulses from the motor cortex that irradiate to autonomic neurons in the brain stem and that its activation establishes, at the onset of exercise, a basal level of sympathetic and parasympathetic efferent activity closely linked to the intensity of the exercise performed. Then, this basic autonomic activity is further modulated by the activation of the exercise pressor reflex Whilst it has been demonstrated that exercise pressor reflex activation can regulate the main hemodynamic modulators (i.e., heart rate, cardiac contractility, preload, and afterload; see the exercise pressor reflex paragraph), fewer studies have been conducted on the hemodynamic consequences of central command activation, as most of them focused on HR, blood pressure responses, and sympathetic-parasympathetic balance, while less attention has been put on central hemodynamics. It is well ascertained that central command can increase HR and blood pressure by increasing sympathetic and decreasing parasympathetic tone, respectively; however, there are no investigations demonstrating any effect of central command on cardiac contractility, preload, or afterload. This is also because it is difficult to isolate the hemodynamic adjustments due central command activity from those arising from exercise pressor reflex. Further research is warranted to better characterize this topic. Summing up, central command is a feed-forward mechanism originating from several regions of the brain which modulate autonomic functions on the basis of the motor cortex activation. The typical consequence of its activation is an increase in HR and blood pressure which occurs rapidly at the beginning of exercise. Baroreflex Arterial baroreceptors are located at the medial-adventitial border of blood vessels in the carotid sinus bifurcation and aortic arch. They are pivotal in inducing the rapid adjustments that occur during acute cardiovascular stress via control over HR and peripheral vascular responses to changes in arterial pressure Blood Pressure Regulation during Exercise. Since the 1960s, the effect of exercise on the arterial baroreflex function has been reported by many investigators Why Is Baroreflex Resetting Important? The "resetting" of the arterial baroreflex is essential to evoke and maintain an effective autonomic nervous system modulation and an adequate cardiovascular adjustment to exercise. In exercising dogs, acute denervation of baroreceptors leads to overnormal increase in arterial blood pressure In other words, if baroreflex function is impaired, then there is an insufficient buffering of the sympathetic tone during exercise. This fact would lead to augmented vasoconstriction and it would lead to a larger increase in blood pressure Functional Sympatholysis and Baroreflex. It has been consistently demonstrated that the full expression of sympathetic activation is metabolically inhibited within exercising tissue Reflexes Interaction during Exercise During exercise, exercise pressor reflex, central command, and baroreflex are all activated and complex interaction occurs between these reflexes. While it is well ascertained that some redundancy and neural occlusion exist between exercise pressor reflex and central command (i.e., their effects do not sum), it is also remarkable that they can all modulate the activity of the other two. The most studied interaction is probably the modulation of baroreflex operated by central command and exercise pressor reflex. In 1990 Rowell and O'Leary [10] proposed a hypothetical scheme of the roles of central command and the exercise pressor reflex in the resetting of the baroreflex during exercise. Subsequently, Raven and colleagues confirmed in a series of experiments this original hypothesis Gallagher et al. [111] assessed the interactive relationship between central command and the exercise pressor reflex for the exercise-induced resetting of carotid baroreflex. In this study, central command and exercise pressure reflex were manipulated by using neuromuscular blockade (vecuronium) and antishock trousers, respectively. Interestingly, exercise-induced baroreflex resetting was greater during the combined enhanced activation of central command and the exercise pressor reflex than during overactivation of either input alone. This finding suggests that central command and the exercise pressor reflex interact. As a consequence, signals from one input facilitate signals from the other, resulting in an accentuated resetting of the baroreflex during exercise. Central command, as a feed-forward mechanism, is likely to be the primary regulator of exercise-induced baroreflex resetting, whereas the exercise pressor reflex operates mainly as a feed-back mechanism. Thus, it exerts a more modulatory role. Furthermore, it seems that both inputs interact and are important for the complete exercise-induced baroreflex resetting The interaction between reflexes clearly appears during postexercise muscle ischemia (PEMI), a method usually employed to study the cardiovascular effects of metaboreflex activation Along with central command and exercise pressor reflex, cardiopulmonary baroreflex can also modulate arterial baroreflex during exercise. Cardiopulmonary baroreflex plays a pivotal role in maintaining the exercise-induced increase in blood pressure Ogoh et al. Conclusions In summary, cardiovascular regulation during exercise is reached through the contemporary integration and interaction between input arising from motor cortex, skeletal muscle receptors, and arterial baroreceptors. While it is well ascertained that baroreflex activity is modulated by both central command and exercise pressor reflex, less is known about the interaction between central command and exercise pressor reflex. Further research in this field is warranted.