New findings r What is the topic for this review?During the exercise recovery period, the combination of centrally mediated decreases in sympathetic nerve activity with a reduced signal transduction from sympathetic nerve activation into vasoconstriction, as well as local vasodilator mechanisms, contributes to the fall in arterial blood pressure seen after exercise. r What advances does it highlight? Important findings from recent studies include the recognition that skeletal muscle afferents may play a primary role in postexercise resetting of the baroreflex via discrete receptor changes within the nucleus tractus solitarii and that sustained postexercise vasodilatation of the previously active skeletal muscle is primarily the result of histamine H 1 and H 2 receptor activation.A single bout of aerobic exercise produces a postexercise hypotension associated with a sustained postexercise vasodilatation of the previously exercised muscle. Work over the last few years has determined key pathways for the obligatory components of postexercise hypotension and sustained postexercise vasodilatation and points the way to possible benefits that may result from these robust responses. During the exercise recovery period, the combination of centrally mediated decreases in sympathetic nerve activity with a reduced signal transduction from sympathetic nerve activation into vasoconstriction, as well as local vasodilator mechanisms, contributes to the fall in arterial blood pressure seen after exercise. Important findings from recent studies include the recognition that skeletal muscle afferents may play a primary role in postexercise resetting of the baroreflex via discrete receptor changes within the nucleus tractus solitarii and that sustained postexercise vasodilatation of the previously active skeletal muscle is primarily the result of histamine H 1 and H 2 receptor activation. Future research directions include further exploration of the potential benefits of these changes in the longer term adaptations associated with exercise training, as well as investigation of how the recovery from exercise may provide windows of opportunity for targeted interventions in patients with hypertension and diabetes.

Recovery from exercise refers to the time period between the end of a bout of exercise and the subsequent return to a resting or recovered state. It also refers to specific physiological processes or states occurring after exercise that are distinct from the physiology of either the exercising or the resting states. In this context, recovery of the cardiovascular system after exercise occurs across a period of minutes to hours, during which many characteristics of the system, even how it is controlled, change over time. Some of these changes may be necessary for long-term adaptation to exercise training, yet some can lead to cardiovascular instability during recovery. Furthermore, some of these changes may provide insight into when the cardiovascular system has recovered from prior training and is physiologically ready for additional training stress. This review focuses on the most consistently observed hemodynamic adjustments and the underlying causes that drive cardiovascular recovery and will highlight how they differ following resistance and aerobic exercise. Primary emphasis will be placed on the hypotensive effect of aerobic and resistance exercise and associated mechanisms that have clinical relevance, but if left unchecked, can progress to symptomatic hypotension and syncope. Finally, we focus on the practical application of this information to strategies to maximize the benefits of cardiovascular recovery, or minimize the vulnerabilities of this state. We will explore appropriate field measures, and discuss to what extent these can guide an athlete's training.

We demonstrate that lower limb heating acutely improves macro- and microvascular dilator function within the atherosclerotic prone vasculature of the leg in aged adults. These findings provide evidence for a potential therapeutic use of chronic lower limb heating to improve vascular health in primary aging and various disease conditions.

Syncope which occurs suddenly in the setting of recovery from exercise, known as post-exercise syncope, represents a failure of integrative physiology during recovery from exercise. We estimate that between 50 and 80% of healthy individuals will develop pre-syncopal signs and symptoms if subjected to a 15-min head-up tilt following exercise. Post-exercise syncope is most often neurally mediated syncope during recovery from exercise, with a combination of factors associated with post-exercise hypotension and loss of the muscle pump contributing to the onset of the event. One can consider the initiating reduction in blood pressure as the tip of the proverbial iceberg. What is needed is a clear model of what lies under the surface; a model that puts the observational variations in context and provides a rational framework for developing strategic physical or pharmacological countermeasures to ultimately protect cerebral perfusion and avert loss of consciousness. This review summarizes the current mechanistic understanding of post-exercise syncope and attempts to categorize the variation of the physiological processes that arise in multiple exercise settings. Newer investigations into the basic integrative physiology of recovery from exercise provide insight into the mechanisms and potential interventions that could be developed as countermeasures against post-exercise syncope. While physical counter maneuvers designed to engage the muscle pump and augment venous return are often found to be beneficial in preventing a significant drop in blood pressure after exercise, countermeasures that target the respiratory pump and pharmacological countermeasures based on the involvement of histamine receptors show promise.

Key pointsr Plasma hyperosmolality delays the onset for sweat production and cutaneous vasodilatation during heat stress in humans; however, the mechanism by which hyperosmolality exerts this effect remains unknown.r This study examined if plasma hyperosmolality exerts a central and/or peripheral modulation of thermoregulatory function in humans.r The main findings are that plasma hyperosmolality delays the increase in skin sympathetic nerve activity during whole-body passive heat stress in humans. In contrast, local intradermal infusion of hyperosmotic saline did not affect sweating or cutaneous vasodilatation.r These results suggest that plasma hyperosmolality delays the onset threshold for sweating and cutaneous vasodilatation by inhibiting efferent thermoregulatory activity in humans.Abstract In humans, plasma hyperosmolality delays the onset of sweating and cutaneous vasodilatation during heat stress. However, it remains unknown if hyperosmolality exerts this effect through a central (i.e. CNS) and/or peripheral (i.e. effector organ) modulation of thermoregulatory activity. We examined if intravenous infusion of hyperosmotic saline affects skin sympathetic nerve activity (SSNA) during whole-body passive heating in healthy humans. Furthermore, we examined if local intradermal infusion of hyperosmotic saline affects sweating and cutaneous vasodilatation during passive heating. Following intravenous infusion of either 0.9% (ISO) or 3.0% (HYPER) NaCl saline, 12 subjects were passively heated until core temperature increased by ß0.6°C. During each condition, sweating and cutaneous vascular conductance were measured over two intradermal microdialysis probes, one perfused with ISO saline and the other with HYPER saline. Intravenous infusion of HYPER saline increased plasma osmolality (294 ± 3 to 316 ± 5 mOsm kg -1 H 2 O, P ࣘ 0.01), which remained greater than ISO throughout heating. Plasma hyperosmolality delayed the mean body temperature onset of sweating (+1.24 ± 0.18 vs. +1.60 ± 0.18°C, P ࣘ 0.01) and cutaneous vasodilatation (+1.15 ± 0.18 vs. +1.53 ± 0.22°C, P ࣘ 0.01), and attenuated the increase in SSNA during heating (+147 ± 178 vs. +427 ± 281%, P ࣘ 0.01). Intradermal infusion of HYPER saline increased baseline cutaneous vascular conductance (P ࣘ 0.01), which did not increase further during the subsequent heating period (P = 0.11). In contrast, intradermal infusion of HYPER saline did not affect sweating (P = 0.99). These results provide direct evidence that plasma hyperosmolality exerts a central modulatory effect governing efferent thermoregulatory activity in humans. Abbreviations HYPER, hyperosmotic; ISO, iso-osmotic; SSNA, skin sympathetic nerve activity.

Altered systemic hemodynamics following exercise can compromise cerebral perfusion and result in syncope. As the Wingate anaerobic test often induces pre-syncope, we hypothesized that a modified Wingate test could form the basis of a novel model for the study of post-exercise syncope and a test-bed for potential countermeasures. Along these lines, breathing through an impedance threshold device has been shown to increase tolerance to hypovolemia, and could prove beneficial in the setting of post-exercise syncope. Therefore, we hypothesized that a modified Wingate test followed by head-up tilt would produce post-exercise syncope, and that breathing through an impedance threshold device (countermeasure) would prevent post-exercise syncope in healthy individuals. Nineteen recreationally active men and women underwent a 60° head-up tilt during recovery from the Wingate test while arterial pressure, heart rate, end-tidal CO2, and cerebral tissue oxygenation were measured on a control and countermeasure day. The duration of tolerable tilt was increased by a median time of 3 min 48 sec with countermeasure compared to control (P < 0.05) and completion of the tilt test increased from 42% to 67% with countermeasure. During the tilt, mean arterial pressure was greater (108.0 ± 4.1 vs.100.4 ± 2.4 mmHg; P < 0.05) with countermeasure compared to control. These data suggest that the Wingate syncope test produces a high incidence of pre-syncope which is sensitive to countermeasures such as inspiratory impedance.

In humans, acute aerobic exercise elicits a sustained postexercise vasodilation within previously active skeletal muscle. This response is dependent on activation of histamine H and H receptors, but the source of intramuscular histamine remains unclear. We tested the hypothesis that interstitial histamine in skeletal muscle would be increased with exercise and would be dependent on de novo formation via the inducible enzyme histidine decarboxylase and/or mast cell degranulation. Subjects performed 1 h of unilateral dynamic knee-extension exercise or sham (seated rest). We measured the interstitial histamine concentration and local blood flow (ethanol washout) via skeletal muscle microdialysis of the vastus lateralis. In some probes, we infused either α-fluoromethylhistidine hydrochloride (α-FMH), a potent inhibitor of histidine decarboxylase, or histamine H/H-receptor blockers. We also measured interstitial tryptase concentrations, a biomarker of mast cell degranulation. Compared with preexercise, histamine was increased after exercise by a change (Δ) of 4.2 ± 1.8 ng/ml ( < 0.05), but not when α-FMH was administered (Δ-0.3 ± 1.3 ng/ml, = 0.9). Likewise, local blood flow after exercise was reduced to preexercise levels by both α-FMH and H/H blockade. In addition, tryptase was elevated during exercise by Δ6.8 ± 1.1 ng/ml ( < 0.05). Taken together, these data suggest that interstitial histamine in skeletal muscle increases with exercise and results from both de novo formation and mast cell degranulation. This suggests that exercise produces an anaphylactoid signal, which affects recovery, and may influence skeletal muscle blood flow during exercise. Blood flow to previously active skeletal muscle remains elevated following an acute bout of aerobic exercise and is dependent on activation of histamine H and H receptors. The intramuscular source of histamine that drives this response to exercise has not been identified. Using intramuscular microdialysis in exercising humans, we show both mast cell degranulation and formation of histamine by histidine decarboxylase contributes to the histamine-mediated vasodilation that occurs following a bout of aerobic exercise.

Author Contributions: Drs Gagnon and Crandall had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.