The skeletal muscle circulation mirrors the varied central hemodynamic alterations, due to dehydration, at rest and during isolated-limb and strenuous whole-body exercise. At rest, limb vascular conductance and limb blood flow (LBF) are enhanced with progressive dehydration, a response maintained during small muscle mass exercise, despite substantial body mass losses (~3.5%) and reductions in limb perfusion pressure (Fig. 4) (36). Conversely, during prolonged, whole-body exercise, the substantial fall in stroke volume (47 mL·beat−1) and Q[Combining Dot Above] (~4 L·min−1) is coupled to an approximately 2 L·min−1 reduction in LBF versus control exercise (11). The marked fall in active limb perfusion during whole-body exercise is offset when fluid intake matches fluid loss (11,28) and when central hemodynamics are normalized by exercising in a supine or semirecumbent position, despite marked body hyperthermia (27,29). Collectively, these studies highlight that the LBF and central hemodynamic responses to dehydration are coupled, such that reductions in LBF are only seen when Q[Combining Dot Above] declines.
A number of putative mechanisms might explain these divergent limb hemodynamic responses to dehydration under resting and different exercise conditions. At rest, the dehydration-induced elevation in limb vascular conductance and LBF (Fig. 4) likely is related in part to thermosensitive mechanisms, responding to changes in internal and local tissue temperature, similar to that observed during local and whole-body passive heating (5,6,19,37). The disparate LBF responses to small muscle mass and whole-body exercise could be related to alterations in either perfusion pressure or local vascular conductance. In this regard, the increase in LBF seen in small muscle mass exercise must be due to net local vasodilation, because mean arterial and limb perfusion pressure is suppressed (36). Furthermore, systemic sympathetic activity was only slightly elevated on the transition from rest to exercise, among the full range of dehydration conditions (e.g., circulating noradrenaline increased from 1 to a peak of 2 nmol·L−1). During whole-body prolonged exercise, a similar fall in mean arterial pressure (~8%) was seen, but circulating catecholamines markedly were elevated (~18 nmol·L−1). Nevertheless, increased sympathetic vasoconstrictor activity did not explain the fall in active-limb perfusion, because vascular conductance was essentially unchanged or slightly enhanced (11,36). However, the progressive decline in Q[Combining Dot Above] and perfusion pressure accounts for most of the reduced end-exercise LBF. This observation is similar to those seen during constant-load, maximal exercise with superimposed body hyperthermia (12). Thus, during strenuous whole-body exercise, reductions in Q[Combining Dot Above] and mean arterial pressure are related to the fall in active-muscle perfusion with dehydration.
The findings from our recent studies indicate that the cardiovascular strain induced by dehydration also has consequences for the cerebral circulation. Regional and global CBF increases on the transition from rest to moderate-intensity exercise (20,35), remaining stable throughout the duration of moderate-intensity exercise (33). However, if exercise intensity progresses beyond approximately 60% V˙O2max, or when constant load exercise is performed in an uncompensable hot environment, CBF is suppressed toward or below baseline levels (33,41). Our experimental findings indicate that dehydration, concomitant to an elevated body core temperature (~1°C), further enhances the cerebrovascular strain by reducing CBF to a similar end-exercise value, equivalent to control conditions, but at a substantially reduced absolute work rate (~270 vs ~340 W), during whole-body cycling exercise (Fig. 5) (48). This advancement of the fall in CBF was not present before dehydration, or after 1 h of recovery with full fluid replenishment, where CBF dynamics were restored to those in the control exercise bout. The independent effect of dehydration was confirmed further when the same participants recorded CBF dynamics comparable with that observed in the control and rehydration tests, during three similar graded exercise bouts, performed on the same day, while fully hydrated. As outlined in Figure 1, the deleterious impact of dehydration on CBF is not isolated to short-duration incremental exercise. We found that during approximately 2 h of prolonged submaximal exercise, without regular fluid ingestion, CBF progressively was suppressed, whereas blood flow to other vessels across the head (e.g., the common- and external-carotid arteries) was comparable with those seen during prolonged exercise while hydrated (47). The dehydration-induced suppression of CBF during prolonged submaximal exercise is similar to the decline seen with substantial elevations in body core temperature (32,33). It is apparent therefore that dehydration compromises CBF during strenuous prolonged and maximal incremental exercise to volitional exhaustion.
Numerous mechanisms, acting independently or synergistically, are purported to regulate the CBF response to exercise (34). Like other vascular beds, perfusion of the cerebral circulation depends on the balance between perfusion pressure and local vascular conductance; it is, however, unlikely that mean arterial pressure per se accounts for the changes in cerebral perfusion during exercise (43). However, and consistent with the available literature, strenuous exercise is coupled to a fall in cerebrovascular conductance, concomitantly to elevations in internal temperature and reductions in the carbon dioxide tension in arterial blood (PaCO2) (47,48); the latter a potent substance invoking both vasodilation (increase PaCO2) and vasoconstriction (decrease PaCO2) across the cerebral circulation (50). Of note, in our present manipulations of hydration status, was that body core temperature was elevated (~1°C) when dehydration developed during prolonged, submaximal and maximal incremental exercise, versus control (hydrated) exercise. It has been shown that body hyperthermia induces nonmetabolic hyperventilation (49) that in turn lowers PaCO2 and CBF (3,26,33,38); restoring PaCO2, while hyperthermic, restores cerebral hemodynamics, even with high levels of minute ventilation (21,26). Thus, dehydration promotes body hyperthermia and decreases CBF, at least in part by a hyperthermic-hyperventilatory reduction in PaCO2.
An important function of the cardiovascular system during exercise is to match active muscle O2 delivery to metabolic demand (1,8,17,18). Manipulation of arterial O2 content (CaO2) leads to concurrent and reciprocal changes in LBF and Q˙ that preserve limb aerobic metabolism, indicating an important role of O2 sensing pathways in blood flow regulation (17). As such, despite the dehydration-induced fall in LBF during prolonged whole-body exercise, limb O2 delivery and aerobic metabolism are, for the most part, maintained due to a widening of the arterial-venous O2 difference and arterial hemoconcentration (11). At rest and during isolated-limb exercise, with a stable limb aerobic metabolism, a small hemoconcentration induced by dehydration might be expected to be accompanied by a reduced LBF. However, both LBF and CaO2 were elevated by dehydration and possibly the effect of exercise per se (36). Because our LBF measures did not discriminate between the different tissues of the limb (e.g., the skin, bone, and muscle), the uncoupling between LBF and CaO2 is likely due to pathways sensing other stimuli such as local tissue and core temperature. Notwithstanding, the differing LBF responses at rest and during small and large muscle mass exercise are met by reciprocal alterations in O2 content and extraction that maintains active muscle aerobic metabolism. However, under intense physiological load (severe exercise, high skin and core temperatures, and substantial dehydration), these adjustments may not compensate for the fall in limb O2 delivery (12).
A relevant question is whether this circulatory challenge to the brain is conducive to a compromised cerebral tissue metabolism. It has been suggested that reductions in CBF impair cerebral oxygenation, which might contribute to fatigue during strenuous exercise (39). However, our experimental work indicates that the cerebral metabolic rate for oxygen (CMRO2) remains remarkably stable across a range of hydration states, exercise intensities, and rest-to-exercise transitions (Fig. 5). Reciprocal elevations in O2 extraction served to compensate for the approximately 18% fall in CBF (13,47,48). Although we acknowledge that global measures of CMRO2 are an imperfect assessment of regional cerebral metabolism (and metabolism of other substrates), and that it remains theoretically possible that substantial reductions in CBF (to the order of >50%) could compromise cerebral oxygenation (2,43), the stable aerobic metabolism of the brain suggests that other circulatory factors (e.g., LBF) play a greater role in the compromised whole-body exercise capacity when dehydrated.
Our model highlights that progressive exercise-induced dehydration, with concomitant hyperthermia, can lead to impaired perfusion to multiple regional tissues and organs. However, the extent of the impact of dehydration on physiological function depends on the level of dehydration, the exercise intensity, and the ambient environmental conditions. Blood flow through the heart, active muscles, and brain is elevated with dehydration at rest and during isolated-muscle or low-intensity exercise. However, during strenuous or prolonged whole-body exercise (>60% V˙O2max), brain, active muscle, and systemic blood flow is compromised, mechanistically associated to an enhanced vasoconstrictor activity, suppressed venous return, and cardiac filling. The fall in regional and systemic perfusion has differing effects on tissue metabolism. However, reductions in active muscle blood flow, which are not compensated fully by elevations in O2 extraction when exercise requires aerobic capacity or close to it, are a likely precursor to early fatigue. Future research should address how fluid- and thermosensitive mechanisms influence the functioning of the human brain, heart, skin, and muscles across exercise domains. Additional research is needed to quantify the limits of the circulatory adjustments across the human brain, among a wider range of hydration and temperature manipulations, to explore any possible association with the onset of fatigue.
The primary studies contained within this manuscript were supported by a grant from the Gatorade Sports Science Institute, PepsiCo Inc, USA. The views contained within this document are those of the authors and do not necessarily reflect those of PepsiCo Inc.
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