Articles in PresS. J Appl Physiol (February 2, 2017). doi:10.1152/japplphysiol.00802.

2016

Romero, Minson, & Halliwill The Cardiovascular System after Exercise 1

3 The Cardiovascular System after Exercise

5 Steven A. Romero1, Christopher T. Minson2, and John R. Halliwill2*

6
1
7 University of Texas Southwestern Medical Center, Dallas, TX, 75235, USA and the Institute for
8 Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, TX, 75231,

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9 USA
2
10 Department of Human Physiology, University of Oregon, Eugene, OR, 97403-1240, USA

11

12 *Corresponding author

13

14 Running Head: The Cardiovascular System after Exercise

15 Keywords: blood pressure, heart rate, blood flow, recovery, athletic performance

16 Word count: 4101

17 Figures: 1

18 Tables: 1

19 References: 83

20 Address for correspondence:

21 John R. Halliwill, PhD
22 122 Esslinger Hall
23 1240 University of Oregon
24 Eugene, OR 97403-1240
25 (541) 346-2841 fax
26 (541) 600-4337 phone
27 halliwil@uoregon.edu

Copyright © 2017 by the American Physiological Society.

 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 2

28 Abstract

29 Recovery from exercise refers to the time period between the end of a bout of
30 exercise and the subsequent return to a resting or recovered state. It also refers to
31 specific physiological processes or states, occurring after exercise, which are distinct
32 from the physiology of either the exercising or the resting states. In this context,
33 recovery of the cardiovascular system after exercise occurs across a period of minutes
34 to hours, during which many characteristics of the system, even how it is controlled, are
35 changing over time. Some of these changes may be necessary for long-term adaptation
36 to exercise training, yet some can lead to cardiovascular instability during recovery.
37 Further, some of these changes may provide insight into when the cardiovascular

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38 system has recovered from prior training and is physiologically ready for additional
39 training stress. This review focuses on the most consistently observed hemodynamic
40 adjustments and the underlying causes that drive cardiovascular recovery and will
41 highlight how they differ following resistance and aerobic exercise. Primary emphasis
42 will be placed on the hypotensive effect of aerobic and resistance exercise and
43 associated mechanisms that have clinical relevance, but if left unchecked, can progress
44 to symptomatic hypotension and syncope. Finally, we will focus on the practical
45 application of this information to strategies to maximize the benefits of cardiovascular
46 recovery, or minimize the vulnerabilities of this state. We will explore appropriate field
47 measures, and discuss to what extent these can guide an athlete’s training.
48
49
50 Abbreviations list

51 Histidine decarboxylase, HDC

52
 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 3

53 Introduction

54 Recovery from exercise refers to the time period between the end of a bout of exercise
55 and the subsequent return to a resting or recovered state. It also refers to specific physiological
56 processes or states, occurring after exercise, which are distinct from the physiology of either the
57 exercising or the resting states (44). In this context, recovery of the cardiovascular system after
58 exercise occurs across a period of minutes to hours, recognized early on in Hill’s initial
59 observations on blood pressure responses following aerobic exercise (35).

60 What is the importance of studying the cardiovascular system during the recovery from
61 exercise? Recovery of the cardiovascular system following exercise is not simply a return to
62 pre-exercise; rather, it is a dynamic period where many physiological changes occur. While

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63 exercise is a critical stress for driving the beneficial cardiovascular adaptations associated with
64 routine physical activity, it is during the recovery period in which these adaptations take place.
65 Some of these changes observed in recovery may be necessary for long-term adaptation to
66 exercise training, yet some can lead to cardiovascular instability during recovery. Thus, it could
67 be argued that the recovery period is equally important as the exercise stimulus. Further, some
68 of these changes during recovery from exercise may provide insight into when the
69 cardiovascular system has recovered from prior training and is physiologically ready for
70 additional training stress.

71 Over the latter part of the last century, our understanding of the cardiovascular system in
72 recovery from exercise grew modestly. However, over the last two decades, many intricacies of
73 recovery have been uncovered through mechanistic studies, often performed in humans, and
74 the growth of knowledge in this area has been strong (24). This work has focused largely on
75 measureable and clinically relevant outcomes (e.g. blood pressure), the mechanisms that
76 control and regulate these outcomes, and the situations and conditions in which the
77 measureable outcomes differ (due to competing or mitigating influences).

78 Given the depth and breadth of current information on this topic and the recency of
79 several reviews (23, 24, 38, 45, 47), this review will focus on the hemodynamic adjustments and
80 underlying mechanisms that occur in response to acute bouts of aerobic versus resistance
81 exercise, with most attention on those adjustments which are sustained for more than 20 min
82 post-exercise. We will explore the potential for practical application of this information to
83 strategies that maximize the benefits of cardiovascular recovery, or minimize the vulnerabilities
 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 4

84 of this state (27), and we will discuss appropriate field measures and the extent that these can
85 guide an athlete’s training.

86 Arterial Pressure as a Key Outcome Variable

87 Arterial blood pressure is one of the most extensively studied hemodynamic variables
88 following exercise, and much of the literature on cardiovascular recovery following exercise has
89 focused on post-exercise hypotension. Arterial pressure is arguably the most highly regulated
90 cardiovascular variable, yet following whole-body aerobic exercise of moderate duration and
91 intensity there is a sustained reduction in arterial pressure. This hemodynamic change has been
92 referred to as post-exercise hypotension (23, 24, 38, 47), and has been observed following both
93 aerobic and resistance exercise.

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94 This is not to suggest that both modes of exercise produce the same cardiovascular
95 response, but to recognize that some aspects, such as reduced pressure, may be common in
96 recovery from many forms of exercise. In its simplest model, arterial pressure is the product of
97 arterial inflow (cardiac output) divided by ease of outflow (systemic vascular conductance, the
98 inverse of total peripheral resistance). Thus, the mechanisms mediating the reduction in arterial
99 pressure following exercise can be dissected by examining the terms in this equation, which can
100 be further reduced to their determinants (e.g., cardiac output can be reduced to heart rate and
101 stroke volume, and venous return can be seen as a determinant of stroke volume, etc).
102 Systemic vascular conductance is determined by the extent of vasoconstriction or vasodilation
103 of individual vascular beds.

104 While arterial pressure is a clinically meaningful measurement and the hallmark of post-
105 exercise hypotension, it is important to note that the reduction in arterial pressure reflects
106 sustained complex adjustments in cardiovascular control, and that some of the responses to
107 exercise appear to be obligatory (consistently observed primary responses to exercise; e.g.
108 arterial baroreflex resetting, histamine release and receptor activation), but others appear to be
109 situational (e.g. reduced preload on the heart can be secondary to fluid loss, elevated body core
110 temperature, changes in body position) (8, 24, 27). Thus, the integration of obligatory
111 components and situational influences can result in minimal (or absent), modest, or severe
112 (symptomatic) hypotension.

113 Cardiovascular Function following Aerobic Exercise

 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 5

114 For the purpose of this review, aerobic exercise will be considered as large or small
115 muscle mass exercise (e.g. cycling, dynamic knee extension) performed for at least 20 min. In
116 general, there is a dose-dependent effect of intensity and duration on the cardiovascular
117 changes following exercise, although there are some inconsistencies in the literature and post-
118 exercise hypotension may be similar across a broad range of intensities and durations (8, 47).
119 These cardiovascular changes also appear following continuous and intermittent exercise,
120 assuming total work is comparable. In general, following whole-body dynamic exercise of
121 moderate duration and intensity, the magnitude of the increase in vascular conductance (or
122 reduction in vascular resistance) is larger than the elevations in cardiac output, meaning that a
123 vasodilation is the driver of the pressure reductions (23). However, in situations such as passive
124 recovery in the upright position, the loss of the muscle pump in the face of gravitational pooling

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125 of blood in the dependent limbs can reduce venous return, central venous pressure, and cardiac
126 preload, resulting in severe hypotension and syncope (26).

127 The persistent vasodilation which underlies post-exercise hypotension lasts several
128 hours, and is known as sustained post-exercise vasodilation. It occurs largely within the
129 vascular beds of previously active skeletal muscle (28) with a lesser contribution from non-
130 active skeletal muscle (15, 30). Notably, vascular conductance in the splanchnic (65),
131 cutaneous (80), and cerebral (81) vascular beds remains unchanged relative to pre-exercise.
132 Halliwill and colleagues were the first to demonstrate that the sustained post-exercise
133 vasodilation is mediated by combined central neural mechanisms (arterial baroreflex resetting)
134 and local vasodilatory mechanisms (28). The arterial baroreflex is shifted downward and to the
135 left, such that that sympathetic activity is reduced despite operating at a lower pressure. This is
136 associated with changes in recovery of heart rate and its beat-to-beat fluctuation (i.e. heart rate
137 variability). While the immediate recovery of heart rate (fast phase) following aerobic exercise is
138 due solely to parasympathetic reactivation, the slow phase of recovery is thought to be due to
139 withdrawal of sympathetic outflow lasting upwards of 90 min post-exercise. (61, 75).

140 Vasodilation within non-active skeletal muscle probably occurs via resetting of the
141 arterial baroreflex and resulting reductions in sympathetic vasoconstrictor tone. Conversely,
142 vasodilation within previously active skeletal muscle results from combined arterial baroreflex
143 resetting, blunted vascular transduction, and the release of local vasodilatory substances. For a
144 thorough review of the specific brain regions, pathways, neurotransmitters, and receptors that
 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 6

145 are involved in mediating the resetting of the arterial baroreflex and associated
146 sympathoinhibition, readers are referred to the excellent work from Chen and Bonham (13).

147 Our understanding of the local dilatory mechanisms of sustained post-exercise

148 vasodilation have been greatly advanced within the last decade by the work of Halliwill and
149 colleagues. Their studies demonstrate that the vasodilation is not dependent on nitric oxide (26),
150 prostanoids (41), or changes in α-adrenergic receptor sensitivity (25), but that histamine (as
151 shown by the use of combined high-dose histamine H1 and H2 receptor antagonists) has an
152 obligatory role as a primary mediator of sustained post-exercise vasodilation (42, 50, 51). The
153 sustained post-exercise vasodilation following 60 min of moderate intensity cycling is inhibited
154 by 80% when histamine receptors are blocked. The remaining 20% which is not affected by
155 histamine blockade is presumed to be the result of resetting of the baroreflex and sympathetic

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156 withdrawal, as it is not apparent following unilateral dynamic knee-extension exercise (3), a
157 model which lacks the baroreflex resetting seen after cycling (10).

158 More recently, Romero and colleagues demonstrated that histamine is elevated in
159 previously active skeletal muscle in humans (74), which is consistent with indirect evidence in
160 rodent models (2, 19, 59, 83). In addition, Romero et al. (74), using skeletal muscle
161 microdialysis, were able to determine that mast cell degranulation and de novo formation via
162 histidine decarboxylase (the enzyme responsible for the conversion of histidine to histamine)
163 contribute to histamine formation and sustained post-exercise vasodilation, a model represented
164 in Figure 1.

165 [FIGURE 1 ABOUT HERE]

166 It is now clear that histamine, formed and released within active skeletal muscle tissue
167 and subsequent activation of histamine H1 and H2 receptors mediates the sustained post-
168 exercise vasodilation. However, the upstream exercise related factor(s) governing this process
169 remain unidentified. Given the dynamic environment within active skeletal muscle, a number of
170 mechanisms have been postulated as the upstream trigger for this pathway to sustained post-
171 exercise vasodilation, including increased temperature, vibration, shear stress, cytokines, and
172 oxidative stress (24). Along these lines, Romero et al. examined if exercise-induced oxidative
173 stress was a necessary contributing factor (72). They found that the systemic infusion of a high-
174 dose antioxidant had no effect on sustained post-exercise vasodilation, suggesting that
175 exercise-induced oxidative stress is not obligatory. To date, the exercise related trigger for
176 histamine release remains elusive.
 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 7

177 Cardiovascular Function following Resistance Exercise

178 For the purpose of this review, we will restrict the discussion of resistance exercise to an
179 acute bout of multiple, whole-body strength exercises (e.g. circuit training). Importantly, the
180 sustained changes in cardiovascular function and underlying mechanisms following these types
181 of whole-body strength routines are distinct from those immediately following a single set of
182 resistance exercise performed by an isolated muscle group (i.e., more muscles groups must be
183 involved to evoke many of the changes to be discussed below).

184 At face value, resistance and aerobic exercise are quite distinct from one another. These
185 differences underlie a number of unique cardiovascular adjustments that occur during
186 resistance exercise which may explain some of the divergent responses following exercise,

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187 when compared to aerobic exercise. Resistance exercise is characterized by intermittent,
188 mostly dynamic exercise that is accompanied by large and rapid swings in arterial blood
189 pressure accompanied by a progressive rise in heart rate (49). In contrast, changes in arterial
190 pressure during aerobic exercise tend to be slight to moderate, and relatively stable.

191 Compared to the wealth of studies investigating hemodynamic adjustments following

192 aerobic exercise, studies investigating cardiovascular function and associated control
193 mechanisms following resistance exercise are fairly limited. However, as highlighted recently by
194 Casonotto (11) the literature is rich with studies investigating the hypotensive effect of
195 resistance exercise and its various permutations. Despite the broad possibilities for what is
196 considered resistance exercise in studies (i.e., the many variations on movements, repetitions,
197 sets), in general, arterial blood pressure is reduced for up to several hours following resistance
198 exercise, although this is not a universal finding (11, 20, 21, 58). In 1994, Brown et al. (9)
199 provided initial observations on the hypotensive effect of resistance exercise; these findings
200 were later confirmed by MacDougal et al. using intra-arterial measures of blood pressure (48).
201 Rezk et al. further characterized the hemodynamic adjustments mediating post-resistance
202 exercise hypotension. However, in contrast to aerobic exercise, post-exercise hypotension with
203 resistance exercise is largely due to attenuated cardiac output, resulting from reduced stroke
204 volume. Additionally, systemic vascular conductance is reduced, further supporting the notion
205 that the hypotension after resistance exercise is due to central, i.e. cardiac hemodynamics and
206 not peripheral vasodilation, a contrast to the hypotension after aerobic exercise. It is unclear
207 why the mechanisms differ following resistance and aerobic exercise. The divergent cardiac
208 output response following resistance exercise may be related to changes in cardiac sympathetic
 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 8

209 activation and/or arterial baroreflex sensitivity, whereas the attenuated systematic vascular
210 conductance may be related to changes in local vasodilator mechanisms within previously
211 active skeletal muscle. For example, knee-extension exercise that replicates classical
212 resistance training (i.e., 3 sets of 8 repetitions at 80% of maximum) does not generate a
213 sustained histaminergic vasodilation, whereas knee-extension exercise that replicates aerobic
214 training does (3). However, there is likely some overlap in central mechanisms, as combined
215 aerobic and resistance exercise does not further reduce arterial pressure compared to aerobic
216 exercise alone (77). Lastly, we note that sex may influence the hemodynamic balance which
217 underlies hypotension after resistance exercise, as it may be more dependent on vasodilation in
218 women (67). It is unclear why this sex-dependent difference exists, but it may be related to sex-
219 based differences in cardiac morphology and/or variations in sex hormone levels (22, 32). In

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220 the one study to report differences, phase of menstrual cycle was not controlled for (67).

221 The underlying mechanisms, hemodynamic adjustments (e.g., regional vascular

222 changes), and autonomic contributions (e.g., baroreflex resetting) are not as well documented
223 following resistance exercise as they are for aerobic exercise, as summarized in Table 1.
224 However, drawing from studies utilizing non-invasive measures of cardiac vagal tone (i.e. heart
225 rate variability), we can gain some insight into the possible neural/autonomic mechanisms which
226 are attenuating the rise in cardiac output and contributing to the reduced arterial blood pressure
227 following resistance exercise. The pattern of heart rate variability after resistance exercise is
228 consistent with a withdrawal of cardiac vagal tone (39). However, these reductions in cardiac
229 vagal tone and increases in heart rate are insufficient to offset the reduction in stroke volume
230 following resistance exercise (34). Additionally, the ability of the arterial baroreflex to buffer
231 reductions in blood pressure is inhibited due to attenuated cardiovagal baroreflex sensitivity (33,
232 58). To our knowledge, more direct measures of these autonomic adjustments, such as direct
233 recordings of sympathetic nerve activity and assessment of baroreflex resetting, have not been
234 made in humans following resistance exercise. Taken together, these existing data suggest that
235 the mechanisms underlying the hemodynamic adjustments following resistance exercise are
236 due, in part, to central neural adjustments.

237 [TABLE 1 ABOUT HERE]

238 Translation from the Lab to the Field: What Matters?

239 As highlighted recently by Luttrell and Halliwill (44), the recovery from exercise can be
240 viewed as a vulnerable period in which individuals are at heightened risk for adverse events, or
 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 9

241 a window of opportunity in which the positive adaptations to training can be manipulated and
242 potentially augmented. Further, it may provide insight into when the cardiovascular system has
243 recovered from prior training and is physiologically ready for additional training stress. Some of
244 these research perspectives are readily translated to coaches and athletes, but others have yet
245 to reach their translational potential.
246 1. Limiting the vulnerability to symptomatic hypotension and syncope.
247 Cardiovascular vulnerability following exercise often presents as post-exercise syncope, the
248 development of pre-syncopal signs and symptoms such as lightheadedness, tunnel vision,
249 blurred vision, etc., or loss of consciousness following either aerobic and resistance exercise
250 (16, 27, 40, 56, 71, 76). Generally, post-exercise syncope is neurogenically mediated and is
251 related to an exaggerated expression of the processes discussed above for post-exercise

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252 hypotension, such as sustained peripheral vasodilation and reduced cardiac preload, which can
253 be made worse by the loss of the muscle pump, upright posture, and hot environmental
254 conditions (27).
255 A number of approaches exist that can prevent post-exercise syncope (27); however,
256 some common medical strategies for treating recurrent syncope (e.g., use of beta-adrenergic
257 blockers and implantable pacemakers) are ill-advised for post-exercise syncope, especially in
258 sport or competitive settings. One pharmacological approach that is worth exploring in
259 individuals with recurrent post-exercise syncope is the use of anti-histamines (52).
260 Active recovery is arguably the most easily implemented and most effective recovery
261 strategy that can prevent post-exercise syncope. Active recovery prevents post-exercise
262 syncope by enhancing venous return in augmenting cardiac preload through rhythmic
263 contractions of skeletal muscle (i.e. the muscle pump). This may be the best justification for
264 performing a cool down after intense exercise. There are also a number of effective physical
265 countermeasures, such as squatting and muscle tensing (79), that can be easily implemented
266 after various sport or athletic events, even those in which active recovery may be difficult (e.g.,
267 stuck at a finish line with no room to move, 84). Leg compression, implemented by compression
268 garments or pneumatic systems can potentially be of help (66).
269 In addition, fluid replacement, particularly in hot and humid conditions, can be
270 considered a basic step to reduce vulnerability to post-exercise syncope. In one case report,
271 ingesting 1 L of water 15 min prior to exercise has been shown to be effective in preventing
272 post-exercise syncope (78), but this volume of fluid ingestion may not be well tolerated by
273 athletes. Water consumption during exercise that approximates sweat loss can may be more
 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 10

274 practical, and increases blood pressure and cardiac output (46) during the recovery from
275 exercise. Post-exercise fluid replacement, particularly those designed to target electrolyte
276 deficits, may mitigate post-exercise syncope and also prepare athletes for subsequent exercise
277 bouts or athletic events (14).
278 There is some potential to augment the respiratory pump to reduce the likelihood of
279 post-exercise syncope. Inspiratory resistance breathing was originally developed as a
280 resuscitation tool. By augmenting intrathoracic negative pressure, it increases venous return
281 and cardiac pre-load. Along these lines, Lacewell and colleagues (40) demonstrated that
282 inspiratory resistance improves orthostatic tolerance following a modified Wingate test. While
283 inspiratory resistance breathing shows promise, it has yet to be translated to the field.
284 Body cooling (i.e., cryotherapy, cold water immersion), which has gained widespread

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285 attention as a strategy to enhance exercise recovery, could also serve as a preventative
286 strategy for post-exercise syncope, particularly in hot and humid conditions. Indeed, Wilson et
287 al. demonstrated that skin surface cooling improved orthostatic tolerance in heat stressed
288 humans (82). Notably, this benefit occurred despite elevated body core temperature, suggesting
289 that local cold-induced vasoconstriction mediated improved orthostatic tolerance. There is
290 currently a bit of controversy over whether post-exercise cold water immersion is beneficial to
291 training adaptations or counter-productive, but that is beyond the scope of this review (60, 68–
292 70).
293 2. Exploiting the window of opportunity. Some features of the cardiovascular system
294 after exercise may lend themselves to beneficial manipulation. For example, our group explored
295 the role that sustained post-exercise vasodilation can play in delivering glucose to the previously
296 exercised muscle, at a time when glucose is taken up for glycogen replacement (18, 62, 63). A
297 similar role can be imagined for amino acid delivery during recovery from resistance exercise.
298 Others have suggested that post-exercise hypotension facilitates the restoration of plasma
299 volume after aerobic exercise (31), even in the absence of fluid replacement. To date, these
300 concepts have yet to be translated into novel training interventions, but the potential seems
301 high.
302 We recently found that the histamine signal associated with exercise has a profound
303 impact on the transcriptome response to exercise (73), suggesting that manipulation of when
304 and for how long this signal is active may potentiate some of the positive training adaptations
305 associated with exercise. That said, we are only beginning to understand the breadth of the
306 transcriptome response, including which aspects are necessary, which are counterproductive,
 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 11

307 and what to target for intervention. More is not always better. Along these lines, we found that
308 histamine blockade prior to muscle damaging exercise (downhill running) increased serum
309 creatine kinase (a marker of muscle damage), and yet resulted in less muscle soreness and
310 more retention of muscle strength during the period of delayed onset muscle soreness (17). To
311 some, the risk of greater muscle damage may be worth the advantages of reduced discomfort
312 and preservation from loss of strength.
313 3. Readiness for additional training stress. What can assessment of the
314 cardiovascular system after exercise tell us about recovery from prior training, and physiological
315 readiness for additional training stress? Perhaps a more important question, which we think is
316 seldom considered, is whether the cardiovascular system needs a recovery period after aerobic
317 or resistance exercise, or whether we are more limited by the recovery time needed by skeletal

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318 muscle to adapt, or energy stores to be replaced. Aside from the fluid losses from the vascular
319 space that need to be replaced following exercise, does the human heart fatigue and need
320 recovery time?
321 Several studies have now reported that after marathon and ultramarathon running
322 events, evidence of cardiac fatigue in the form of diastolic dysfunction is present in some
323 runners (more often men than women) (12, 36, 37, 43, 54, 55, 57). However, this does not
324 appear to be the case following most forms of aerobic exercise, and it seems fair to say there is
325 no deficit in cardiovascular function for most exercisers after a single bout of aerobic or
326 resistance exercise. Thus, we shift the question to whether assessment of the cardiovascular
327 system after exercise tells us about recovery of other systems from prior training, and
328 physiological readiness of those other systems for additional training stress. Along these lines,
329 resting heart rate and heart rate variability are often promoted to athletes and coaches as useful
330 biomarkers of recovery and preparedness.
331 Measuring heart rate is arguably the easiest and most widely utilized tool to assess
332 recovery following exercise. Typically, heart rate measured using a heart rate sensor embedded
333 in a chest strap, but wrist-based sensors are becoming common. Heart rate is usually displayed
334 on a wrist watch or more recently sent to cell phones or tablets using wireless technology.
335 Measurement of heart rate in this fashion is fairly accurate, inexpensive (price range, $50 -
336 $250), and easily implemented.
337 Certain portable heart rate monitors have the capability to assess heart rate variability,
338 which reflects the beat-to-beat fluctuation in heart rate and/or the duration of R wave intervals
339 (5). Heart variability metrics are thought to reflect cardiac autonomic regulation, specifically
 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 12

340 parasympathetic and to a lesser extent sympathetic cardiac control, or some combination
341 thereof (i.e. sympatho-vagal balance) (1, 6). The use of heart rate variability metrics within the
342 context of exercise or sport has dramatically increased since its mainstream inception, probably
343 owing to its low cost and ease of use. In general, heart rate variability follows the same temporal
344 pattern as heart rate during recovery from exercise (29, 64).
345 In theory, these cardiac measures could serve as “the canary in the coal mine” for over-
346 reaching and over-training, as they represent the integration of autonomic pathways which are
347 sensitive to a wide range of homeostatic processes. But in general, the research on heart rate
348 and heart rate variability as biomarkers of recovery during long-term training stress suggests
349 that they fail to live up to this promise (4, 7, 53). Away from the confines of a controlled
350 laboratory environment and strict experimental guidelines, caution should be used when using

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351 heart rate or its variability to assess cardiac autonomic control or recovery from exercise or
352 sport. Rather, an integrated approach should be utilized beyond the immediate recovery period
353 and include other markers of overreaching or overtraining, such as generalized fatigue,
354 plateaued or declining performance, sleeplessness, irritability, an inability to attain higher heart
355 rates during training, etc.

356 Conclusions

357 The cardiovascular system after exercise exists in a physiologic state which differs from
358 both rest and exercise. It has a physiology of its own, including the phenomena of post-exercise
359 hypotension, sustained post-exercise vasodilation, and activation of a histamine signaling
360 pathway of undefined consequence. The hemodynamic adjustments that occur during the
361 recovery from aerobic and resistance exercise are driven by highly coordinated and controlled
362 mechanisms. However, if left unchecked, these adjustments can progress to cardiovascular
363 instability. The future likely will include training methods which take advantage of the processes
364 present in the cardiovascular system after exercise, and it may yet provide a window into
365 recovery and readiness for training stress.

366
 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 13

367 References

368 1. Akselrod S, Gordon D, Ubel FA, Shannon DC, Barger AC, Cohen RJ. Power
369 spectrum analysis of heart rate fluctuation: a quantitative probe of beat-to-beat
370 cardiovascular control. Science 213: 220–222, 1981.

371 2. Ayada K, Watanabe M, Endo Y. Elevation of histidine decarboxylase activity in skeletal

372 muscles and stomach in mice by stress and exercise. Am J Physiol Regul Integr Comp
373 Physiol 279: R2042-R2047, 2000.

374 3. Barrett-O’Keefe Z, Kaplon RE, Halliwill JR. Sustained post-exercise vasodilatation and
375 histamine-receptor activation following small muscle-mass exercise in humans. Exp
376 Physiol 98: 268–277, 2013.

Downloaded from http://jap.physiology.org/ by 10.220.32.247 on February 6, 2017

377 4. Bellenger CR, Fuller JT, Thomson RL, Davison K, Robertson EY, Buckley JD.
378 Monitoring athletic training status through autonomic heart rate regulation: A systematic
379 review and meta-analysis. Sports Med. ( February 18, 2016). doi: 10.1007/s40279-016-
380 0484-2.

381 5. Billman GE. Heart rate variability - a historical perspective. Front Physiol 2: 86, 2011.

382 6. Billman GE, Huikuri H V, Sacha J, Trimmel K. An introduction to heart rate variability :
383 methodological considerations and clinical applications. Front Physiol 6: eCollection,
384 2015.

385 7. Bosquet L, Merkari S, Arvisais D, Aubert AE. Is heart rate a convenient tool to monitor
386 over-reaching? A systematic review of the literature. Br J Sports Med 42: 709–14, 2008.

387 8. Brito LC, Queiroz ACC, Forjaz CL. Influence of population and exercise protocol
388 characteristics on hemodynamic determinants of post-aerobic exercise hypotension.
389 Brazil J Med Biol Res 47: 626-636, 2014.

390 9. Brown SP, Clemons JM, He Q, Liu S. Effects of resistance exercise and cycling on
391 recovery blood pressure. J Sport Sci 12: 463–8, 1994.

392 10. Buck TM, Romero SA, Ely MR, Sieck DC, Abdala PM, Halliwill JR. Neurovascular
393 control following small muscle-mass exercise in humans. Physiol Rep 3: e12289–e12289,
394 2015.

395 11. Casonatto J, Goessler KF, Cornelissen VA, Cardoso JR, Polito MD. The blood
 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 14

396 pressure-lowering effect of a single bout of resistance exercise: A systematic review and
397 meta-analysis of randomised controlled trials. Eur J Prev Cardiol 23: 1700-1714, 2016.

398 12. Chan-Dewar F, Oxborough D, Shave R, Gregson W, Whyte G, Noakes T, George K.

399 Evidence of increased electro-mechanical delay in the left and right ventricle after
400 prolonged exercise. Eur J Appl Physiol 108: 581–587, 2010.

401 13. Chen CY, Bonham AC. Postexercise hypotension: Central mechanisms. Exerc Sport Sci
402 Rev 38: 122–127, 2010.

403 14. Cheuvront SN, Kenefick RW. Dehydration: Physiology, assessment, and performance
404 effects. Compr Physiol 4: 257–285, 2014.

405 15. Coats AJ, Conway J, Isea JE, Pannarale G, Sleight P, Somers VK. Systemic and

Downloaded from http://jap.physiology.org/ by 10.220.32.247 on February 6, 2017

406 forearm vascular resistance changes after upright bicycle exercise in man. J Physiol 413:
407 289–298, 1989.

408 16. Compton D, Hill PM, Sinclair JD. Weight-lifters’ blackout. Lancet 2: 1234–1237, 1973.

409 17. Ely MR, Romero SA, Sieck DC, Mangum JE, Luttrell MJ, Halliwill JR. A single dose of
410 histamine-receptor antagonists prior to downhill running alters markers of muscle damage
411 and delayed onset muscle soreness. J Appl Physiol (2016). doi:
412 10.1152/japplphysiol.00518.2016.

413 18. Emhoff CA, Barrett-O’Keefe Z, Padgett RC, Hawn JA, Halliwill JR. Histamine-receptor
414 blockade reduces blood flow but not muscle glucose uptake during postexercise recovery
415 in humans. Exp Physiol 96: 664–673, 2011.

416 19. Endo Y, Tabata T, Kuroda H, Tadano T, Matsushima K, Watanabe M. Induction of

417 histidine decarboxylase in skeletal muscle in mice by electrical stimulation, prolonged
418 walking and interleukin-1. J Physiol 509: 587–598, 1998.

419 20. Fisher MM. The effect of resistance exercise on recovery blood pressure in normotensive
420 and borderline hypertensive women. J Strength Cond Res 15: 210–216, 2001.

421 21. Focht BC, Koltyn KF. Influence of resistance exercise of different intensities on state
422 anxiety and blood pressure. Med Sci Sport Exerc 31: 456–463, 1999.

423 22. Fu Q, Arbab-Zadeh A, Perhonen MA, Zhang R, Zuckerman JH, Levine BD.
424 Hemodynamics of orthostatic intolerance: implications for gender differences. Am J Hear
 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 15

425 Circ Physiol 286: H449-57, 2004.

426 23. Halliwill JR. Mechanisms and clinical implications of post-exercise hypotension in
427 humans. Exerc Sport Sci Rev 29: 65–70, 2001.

428 24. Halliwill JR, Buck TM, Lacewell AN, Romero SA. Postexercise hypotension and
429 sustained postexercise vasodilation: What happens after we exercise? Exp Physiol 98:
430 7–18, 2013.

431 25. Halliwill JR, Dinenno FA, Dietz NM. Alpha-adrenergic vascular responsiveness during
432 postexercise hypotension in humans. J Physiol 550: 279–286, 2003.

433 26. Halliwill JR, Minson CT, Joyner MJ. Effect of systemic nitric oxide synthase inhibition
434 on postexercise hypotension in humans. J Appl Physiol 89: 1830–1836, 2000.

Downloaded from http://jap.physiology.org/ by 10.220.32.247 on February 6, 2017

435 27. Halliwill JR, Sieck DC, Romero SA, Buck TM, Ely MR. Blood pressure regulation X:
436 What happens when the muscle pump is lost? Post-exercise hypotension and syncope.
437 Eur J Appl Physiol 114: 561–578, 2014.

438 28. Halliwill JR, Taylor JA, Eckberg DL. Impaired sympathetic vascular regulation in
439 humans after acute dynamic exercise. J Physiol 495: 279–288, 1996.

440 29. Halliwill JR, Taylor JA, Hartwig TD, Eckberg DL. Augmented baroreflex heart rate gain
441 after moderate-intensity, dynamic exercise. Am J Physiol Regul Integr Comp Physiol 270:
442 R420–R426, 1996.

443 30. Hara K, Floras J. Influence of naloxone on muscle sympathetic nerve activity. J
444 Hypertens 13: 447–461, 1995.

445 31. Hayes PM, Lucas JC, Shi X. Importance of post-exercise hypotension in plasma volume
446 restoration. Acta Physiol Scand 169: 115–124, 2000.

447 32. Hayward CS, Kelly RP, Collins P. The roles of gender, the menopause and hormone
448 replacement on cardiovascular function. Cardiovasc Res 46: 28–49, 2000.

449 33. Heffernan KS, Collier SR, Kelly EE, Jae SY, Fernhall B. Arterial stiffness and
450 baroreflex sensitivity following bouts of aerobic and resistance exercise. Int J Sport Med
451 28: 197–203, 2007.

452 34. Heffernan KS, Kelly EE, Collier SR, Fernhall B. Cardiac autonomic modulation during
453 recovery from acute endurance versus resistance exercise. Eur J Cardiovasc Prev
 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 16

454 Rehabil 13: 80–86, 2006.

455 35. Hill L. Arterial pressure in man while sleeping, resting, working and bathing. J Physiol 22:
456 xxvi–xxx, 1898.

457 36. Jouffroy R, Caille V, Perrot S, Vieillard-Baron A, Dubourg O, Mansencal N. Changes

458 of cardiac function during ultradistance trail running. Am J Cardiol 116: 1284–9, 2015.

459 37. Kasikcioglu E, Arslan A, Topcu B, Sayli O, Akhan H, Oflaz H, Akin A, Kayserilioglu
460 A, Meric M. Cardiac fatigue and oxygen kinetics after prolonged exercise. Int J Cardiol
461 108: 286–8, 2006.

462 38. Kenny MJ, Seals DR. Postexercise hypotension: key features, mechanisms, and clinical
463 significance. Hypertension 22: 653–664, 1993.

Downloaded from http://jap.physiology.org/ by 10.220.32.247 on February 6, 2017

464 39. Kingsley JD, Figueroa A. Acute and training effects of resistance exercise on heart rate
465 variability. Clin Physiol Funct Imaging 36: 179–187, 2016.

466 40. Lacewell AN, Buck TM, Romero SA, Halliwill JR. Post-exercise syncope: Wingate
467 syncope test and effective countermeasure. Exp Physiol 99: 172–186, 2014.

468 41. Lockwood JM, Pricher MP, Wilkins BW, Holowatz LA, Halliwill JR. Postexercise
469 hypotension is not explained by a prostaglandin-dependent peripheral vasodilation. J
470 Appl Physiol 98: 447–453, 2005.

471 42. Lockwood JM, Wilkins BW, Halliwill JR. H1 receptor-mediated vasodilatation
472 contributes to postexercise hypotension. J Physiol 563: 633–642, 2005.

473 43. Lucía A, Serratosa L, Saborido A, Pardo J, Boraita A, Morán M, Bandrés F, Megías
474 A, Chicharro JL. Short-term effects of marathon running: no evidence of cardiac
475 dysfunction. Med Sci Sports Exerc 31: 1414–21, 1999.

476 44. Luttrell MJ, Halliwill JR. Recovery from exercise: vulnerable state, window of
477 opportunity, or crystal ball? Front Physiol 6: 204, 2015.

478 45. Luttrell MJ, Halliwill JR. The intriguing role of histamine in exercise responses. Exerc
479 Sport Sci Rev 45: DOI: DOI: 10.1249/JES.0000000000000093, 2017.

480 46. Lynn BM, Minson CT, Halliwill JR. Fluid replacement and heat stress during exercise
481 alter post-exercise cardiac haemodynamics in endurance exercise-trained men. J Physiol
482 587: 3605–3617, 2009.
 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 17

483 47. MacDonald JR. Potential causes, mechanisms, and implications of post exercise
484 hypotension. J Hum Hyperten 16: 225–236, 2002.

485 48. MacDonald JR, MacDougall JD, Interisano SA, Smith KM, McCartney N, Moroz JS,
486 Younglai E V, Tarnopolsky MA. Hypotension following mild bouts of resistance exercise
487 and submaximal dynamic exercise. Eur J Appl Physiol Occup Physiol 79: 148–54, 1999.

488 49. Macdougall JD, Tuxen D, Sale DG, Moroz JR, Sutton JR. Arterial blood pressure
489 response to heavy resistance exercise. J Appl Physiol 58: 785–790, 1985.

490 50. McCord JL, Beasley JM, Halliwill JR. H2-receptor-mediated vasodilation contributes to
491 postexercise hypotension. J Appl Physiol 100: 67–75, 2006.

492 51. McCord JL, Halliwill JR. H1 and H2 receptors mediate postexercise hyperemia in

Downloaded from http://jap.physiology.org/ by 10.220.32.247 on February 6, 2017

493 sedentary and endurance exercise-trained men and women. J Appl Physiol 101: 1693–
494 1701, 2006.

495 52. McCord JL, Pellinger TK, Lynn BM, Halliwill JR. Potential benefit from an H1-receptor
496 antagonist on postexercise syncope in the heat. Med Sci Sport Exerc 40: 1953–1961,
497 2008.

498 53. Meeusen R, Duclos M, Foster C, Fry A, Gleeson M, Nieman D, Raglin J, Rietjens G,
499 Steinacker J, Urhausen A. Prevention, diagnosis, and treatment of the overtraining
500 syndrome: Joint consensus statement of the european college of sport science and the
501 American College of Sports Medicine. Med Sci Sports Exerc 45: 186–205, 2013.

502 54. Middleton N, Shave R, George K, Whyte G, Forster J, Oxborough D, Gaze D,

503 Collinson P. Novel application of flow propagation velocity and ischaemia-modified
504 albumin in analysis of postexercise cardiac function in man. Exp Physiol 91: 511–9, 2006.

505 55. Montiel G, Horn T, Vafa R, Solera A, Hollmann W, Predel HG, Brinkmann C.
506 Echocardiographic and biochemical analysis of cardiac function and injury among female
507 amateur runners post-marathon. Wien Klin Wochenschr 128: 193–7, 2016.

508 56. Moralez G, Romero SA, Rickards CA, Ryan KL, Convertino VA, Cooke WH. Effects
509 of dehydration on cerebrovascular control during standing after heavy resistance
510 exercise. J Appl Physiol 112: 1875–1883, 2012.

511 57. Neilan TG, Yoerger DM, Douglas PS, Marshall JE, Halpern EF, Lawlor D, Picard MH,
512 Wood MJ. Persistent and reversible cardiac dysfunction among amateur marathon
 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 18

513 runners. Eur Heart J 27: 1079–84, 2006.

514 58. Niemelä TH, Kiviniemi AM, Hautala AJ, Salmi JA, Linnamo V, Tulppo MP. Recovery
515 pattern of baroreflex sensitivity after exercise. Med Sci Sport Exerc 40: 864–70, 2008.

516 59. Niijima-Yaoita F, Tsuchiya M, Ohtsu H, Yanai K, Sugawara S, Endo Y, Tadano T.

517 Roles of histamine in exercise-induced fatigue: favouring endurance and protecting
518 against exhaustion. Biol Pharm Bull 35: 91–97, 2012.

519 60. Peake JM, Markworth JF, Nosaka K, Raastad T, Wadley GD, Coffey VG. Modulating
520 exercise-induced hormesis: does less equal more? J Appl Physiol 119: 172–89, 2015.

521 61. Peçanha T, Bartels R, Brito LC, Paula-Ribeiro M, Oliveira RS, Goldberger JJ.
522 Methods of assessment of the post-exercise cardiac autonomic recovery: A

Downloaded from http://jap.physiology.org/ by 10.220.32.247 on February 6, 2017

523 methodological review. Int J Cardiol (2016). doi: 10.1016/j.ijcard.2016.10.057.

524 62. Pellinger TK, Dumke BR, Halliwill JR. Effect of H1- and H2-histamine receptor
525 blockade on postexercise insulin sensitivity. Physiol Rep 1: e00033, 2013.

526 63. Pellinger TK, Simmons GH, MacLean DA, Halliwill JR. Local histamine H(1-) and H(2)-
527 receptor blockade reduces postexercise skeletal muscle interstitial glucose
528 concentrations in humans. Appl Physiol Nutr Metab 35: 617–626, 2010.

529 64. Piepoli M, Coats AJ, Adamopoulos S, Bernardi L, Feng YH, Conway J, Sleight P.
530 Persistent peripheral vasodilation and sympathetic activity in hypotension after maximal
531 exercise. J Appl Physiol 75: 1807–14, 1993.

532 65. Pricher MP, Holowatz LA, Williams JT, Lockwood JM, Halliwill JR. Regional
533 hemodynamics during postexercise hypotension. I. Splanchnic and renal circulations. J
534 Appl Physiol 97: 2065–2070, 2004.

535 66. Privett SE, George KP, Whyte GP, Cable NT. The effectiveness of compression
536 garments and lower limb exercise on post-exercise blood pressure regulation in
537 orthostatically intolerant athletes. Clin J Sport Med 20: 362–367, 2010.

538 67. Queiroz AC, Rezk CC, Teixeira L, Tinucci T, Mion D, Forjaz CL. Gender influence on
539 post-resistance exercise hypotension and hemodynamics. Int J Sport Med 34: 939–944,
540 2013.

541 68. Roberts LA, Muthalib M, Stanley J, Lichtwark G, Nosaka K, Coombes JS, Peake JM.
 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 19

542 Effects of cold water immersion and active recovery on hemodynamics and recovery of
543 muscle strength following resistance exercise. Am J Physiol Regul Integr Comp Physiol
544 309: R389-98, 2015.

545 69. Roberts LA, Nosaka K, Coombes JS, Peake JM. Cold water immersion enhances
546 recovery of submaximal muscle function after resistance exercise. Am J Physiol Regul
547 Integr Comp Physiol 307: R998–R1008, 2014.

548 70. Roberts LA, Raastad T, Markworth JF, Figueiredo VC, Egner IM, Shield A,
549 Cameron-Smith D, Coombes JS, Peake JM. Post-exercise cold water immersion
550 attenuates acute anabolic signalling and long-term adaptations in muscle to strength
551 training. J Physiol 593: 4285–301, 2015.

Downloaded from http://jap.physiology.org/ by 10.220.32.247 on February 6, 2017

552 71. Romero SA, Cooke WH. Hyperventilation before resistance exercise: cerebral
553 hemodynamics and orthostasis. Med Sci Sport Exerc 39: 1302–1307, 2007.

554 72. Romero SA, Ely MR, Sieck DC, Luttrell MJ, Buck TM, Kono JM, Branscum AJ,
555 Halliwill JR. Effect of antioxidants on histamine receptor activation and sustained
556 postexercise vasodilatation in humans. Exp Physiol 100: 435–499, 2015.

557 73. Romero SA, Hocker AD, Mangum JE, Luttrell MJ, Turnbull DW, Struck AJ, Ely MR,
558 Sieck DC, Dreyer HC, Halliwill JR. Evidence of a broad histamine footprint on the
559 human exercise transcriptome. J Physiol 594: 5009–5023, 2016.

560 74. Romero SA, McCord JL, Ely MR, Sieck DC, Buck TM, Luttrell MJ, MacLean DA,
561 Halliwill JR. Mast cell degranulation, de novo histamine formation, and sustained post-
562 exercise vasodilation in humans. J Appl Physiol (2016). doi:
563 10.1152/japplphysiol.00633.2016.

564 75. Seiler S, Haugen O, Kuffel E. Autonomic recovery after exercise in trained athletes:
565 Intensity and duration effects. Med Sci Sport Exerc 39: 1366–1373, 2007.

566 76. Sieck DC, Ely MR, Romero SA, Luttrell MJ, Abdala PM, Halliwill JR. Post-exercise
567 syncope: Wingate syncope test and visual-cognitive function. Physiol Rep 4: e12883,
568 2016.

569 77. Teixeira L, Ritti-Dias RM, Tinucci T, Mion Júnior D, Forjaz CL. Post-concurrent
570 exercise hemodynamics and cardiac autonomic modulation. Eur J Appl Physiol 111:
571 2069–78, 2011.
 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 20

572 78. Thijs RD, Reijntjes RHAM, van Dijk JG. Water drinking as a potential treatment for
573 idiopathic exercise-related syncope: a case report. Clin Auto Res 13: 103–105, 2003.

574 79. Wieling W, van Dijk N, Thijs RD, de Lange FJ, Krediet CTP, Halliwill JR. Physical
575 countermeasures to increase orthostatic tolerance. J Intern Med 277: 69–82, 2015.

576 80. Wilkins BW, Minson CT, Halliwill JR. Regional hemodynamics during postexercise
577 hypotension. II. Cutaneous circulation. J Appl Physiol 97: 2071–2076, 2004.

578 81. Willie CK, Ainslie PN, Taylor CE, Eves ND, Tzeng Y-C. Maintained cerebrovascular
579 function during post-exercise hypotension. Eur J Appl Physiol 113: 1597–1604, 2013.

580 82. Wilson TE, Cui J, Zhang R, Witkowski S, Crandall CG. Skin cooling maintains cerebral
581 blood flow velocity and orthostatic tolerance during tilting in heated humans. J Appl

Downloaded from http://jap.physiology.org/ by 10.220.32.247 on February 6, 2017

582 Physiol 93: 85–91, 2002.

583 83. Yoneda H, Niijima-Yaoita F, Tsuchiya M, Kumamoto H, Watanabe M, Ohtsu H, Yanai

584 K, Tadano T, Sasaki K, Sugawara S, Endo Y. Roles played by histamine in strenuous
585 or prolonged masseter muscle activity in mice. Clin Exp Pharmacol Physiol 40: 848–55,
586 2013.

587 84. A knockout finish: Advice on preventing a finish-line fainting spell. Run. World: 2004.

588

589
 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 21

590 Funding

591 Funded by the National Institutes of Health Grants HL115027 and GM117693

592 Acknowledgements

593 We would like to thank those individuals who have contributed to our work on exercise recovery
594 over the last decade.

595 Disclosures

596 The authors have no competing interests to declare.

597

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 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 22

598 Table 1. Hemodynamic adjustments during the recovery from aerobic and resistance
599 exercise. Central hemodynamic adjustments are depicted as a change relative to pre-exercise
600 using arrows. Question marks represent hypothesized adjustments for which experimental
601 evidence is not available.
602
Post Aerobic Post Resistance

Mean Arterial Pressure (MAP) ↓ ↓

Cardiac Output (Q) ↑ ↓

Systemic vascular conductance (SVC) ↑↑ ↓

Skeletal Muscle Conductance ↑↑ ?

Splanchnic & Renal Conductances ∼ ?

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Cutaneous Conductance ∼ ?

Cerebral Conductance ∼ ?
603
604
 Romero, Minson, & Halliwill The Cardiovascular System after Exercise 23

605 Figure Legends

606 Figure 1. Sources of Histamine in Skeletal Muscle after Exercise.

607 Mast cell degranulation and de novo formation via histidine decarboxylase (HDC, the enzyme
608 responsible for the conversion of histidine to histamine) contribute to histamine formation and
609 sustained post-exercise vasodilation by activation of histamine H1 and H2 receptors. In addition
610 to vasodilation, histamine has broad effects on the exercise transcriptome (45, 73). Modified
611 from (24).

612

613

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614
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