Dynamic arterial baroreflex function during high intensity exercise in humans: insights into sympathetic control.

The sympathetic nervous system plays a critical role in mediating the cardiovascular adjustments necessary for performing and sustaining exercise including increases in heart rate, stroke volume and arterial blood pressure (BP), and a redistribution of cardiac output to active skeletal muscle. Exercise-induced increases in sympathetic nerve activity (SNA) are mediated by central signals arising from higher brain centres (i.e. central command) and by peripheral feedback from skeletal muscle (i.e. exercise pressor reflex) with important modulation provided by the arterial baroreflex (ABR) (Mitchell, 1990; Raven et al. 2006). Indeed arterial baroreceptors play a pivotal role in the rapid reflex adjustments that accompany acute cardiovascular stressors by buffering beat-to-beat fluctuations in BP via modulation of autonomic neural activity to the heart and vasculature (Joyner, 2006; Raven et al. 2006). During exercise it has been demonstrated that the ABR continues to regulate BP by resetting to operate around the exercise-induced elevation in BP (Raven et al. 2006). Moreover, there is convincing evidence that a properly functioning ABR is requisite for an appropriate neural cardiovascular response to exercise. Previous studies have demonstrated that acute removal of arterial baroreceptor input leads to an exaggerated increase in BP in exercising dogs (Walgenbach & Donald, 1983). Similarly, in humans who have surgically denervated carotid baroreceptors, the BP response to physical stress is exaggerated (Timmers et al. 2004). An emerging concept is that the ABR acts to partially restrain the BP response to exercise by buffering increases in SNA produced by activation of central command and the exercise pressor reflex (Joyner, 2006). This concept is substantiated by the 3-fold greater increase in muscle SNA observed during isometric handgrip in healthy subjects when ABR activation was prevented by pharmacologically clamping BP at resting values and negating the exercise-induced rise in BP (Scherrer et al. 1990). Furthermore, the ABR has been shown to effectively modulate muscle SNA during moderate intensity arm cycling, one-legged kicking and handgrip exercise (Fadel et al. 2001; Ichinose et al. 2006). However, whether these findings can be extrapolated to higher intensities of dynamic exercise using larger muscle masses remained untested until now, primarily because of the associated movement problems and thus the maintenance of quality muscle SNA recordings in humans. In this issue of The Journal of Physiology, Ichinose et al. (2008) completed the arduous and undoubtedly frustrating task of obtaining direct recordings of muscle SNA from the median nerve of the arm during an incremental bout of leg cycling to exhaustion and in so doing provide invaluable information regarding the ability of the ABR to modulate SNA during high intensity dynamic exercise in humans. Ichinose et al. (2008) tested the insightful hypothesis that the ABR control over muscle SNA does not remain constant throughout an incremental bout of leg cycling during which intensity is increased from very mild to exhausting. ABR control of muscle SNA was evaluated by analysing the linear relationship between spontaneously occurring variations in diastolic blood pressure and muscle SNA during very mild, mild, moderate, heavy and exhausting leg cycling. Muscle SNA was quantified as mean burst strength (area), burst incidence (bursts per 100 heart beats) and total muscle SNA (mean burst strength times burst frequency). They found that ABR control of burst strength, burst incidence, and total muscle SNA were all modulated in a time-dependent manner throughout cycling with an initial downward shift in the diastolic blood pressure–muscle SNA relationships during very mild exercise followed by progressive upward and rightward resetting as exercise intensity increased (Figs 2, 3 and 4 in Ichinose et al. 2008). Perhaps more importantly ABR sensitivity (i.e. gain) for the control of total muscle SNA was similar to rest during mild and moderate exercise, but was significantly increased during heavy and exhausting exercise. Collectively, these data demonstrate that in humans a continuous and dynamic resetting of the ABR regulation of muscle SNA occurs during incremental leg cycling to exhaustion with greater control (i.e. increased sensitivity) being exhibited at higher exercise intensities. Aside from the valuable information on the ABR control of sympathetic outflow derived by this study, Ichinose et al. (2008) also shed considerable light on the overall sympathetic response to dynamic exercise in humans. Indeed, from very mild to exhaustive exercise an approximate 8-fold increase in muscle SNA was observed. These data clearly demonstrate the vital role the sympathetic nervous system plays in mediating the cardiovascular adjustments to exercise. Importantly, this tremendous increase in muscle SNA occurred in concert with the progressive resetting of the ABR as well as increased ABR–muscle SNA sensitivity at higher workloads. As suggested by the authors, these time-dependent alterations in ABR function are likely to play an important role in matching the sympathetic and overall cardiovascular responses to exercise intensity. In addition, the continuous alterations in ABR regulation would be expected to play a role in increasing and stabilizing the sympathetic and BP response during exercise. As such, one would expect that impairments in baroreflex function would lead to unchecked elevations in muscle SNA and BP. Undoubtedly these data demonstrate the importance of a properly functioning and dynamically changing ABR control of SNA during large muscle dynamic exercise in humans. Although the mechanism(s) driving the increased sensitivity in baroreflex control of muscle SNA remain incompletely understood, a role for the metabolic component of the exercise pressor reflex (i.e. muscle metaboreflex) has been suggested. This is in line with the most notable changes in sensitivity occurring during the higher intensities of dynamic exercise. Recent findings by Miki et al. (2003) indicate that the intensity of exercise is indeed an important factor. These investigators reported that the sensitivity of the ABR control of renal SNA is increased during high intensity (∼90% maximal heart rate) treadmill exercise in rats. However, considering that a host of other inputs contributing to sympathetic control are also influenced by high workloads of dynamic exercise (e.g. thermoregulation, central command), the mechanism(s) mediating these changes in ABR–SNA sensitivity at high intensities of dynamic exercise require further investigation. In summary, Ichinose and colleagues should be commended on performing these ‘heroic’ experiments elucidating a continuous and dynamic ABR–muscle SNA resetting from very mild to exhaustive leg cycling in humans. The findings of an increase in ABR–muscle SNA gain during higher intensities of exercise further demonstrate the importance of baroreflex restraint of SNA during dynamic exercise. Eightfold increases in muscle SNA with a properly functioning ABR makes one wonder how high SNA goes during exercise when baroreflex function is diminished as with various disease states: a question that awaits future studies.