ARTICLE

Mechanisms and Clinical Implications of

Post-exercise Hypotension in Humans
John R. Halliwill
Department of Anesthesiology and General Clinical Research Center, Mayo Clinic and Foundation, Rochester,
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HALLIWILL, J.R. Mechanisms and clinical implications of post-exercise hypotension in humans. Exerc. Sports Sci. Rev.,
Vol. 29, No. 2, pp. 65-70, 2001. Post-exercise hypotension is common after moderate-intensity dynamic exercise. It results from
persistent reductions in vascular resistance mediated by the autonomic nervous system and vasodilator substances. These effects appear
more pronounced and last longer in hypertensive individuals. Post-exercise hypotension may also play an important role in plasma
volume recovery after exercise. Keywords: sympathetic nervous system, vasodilator agents, blood pressure, nitric oxide,
hypertension, post-exercise, orthostatic

INTRODUCTION OVERVIEW OF HEMODYNAMIC CHANGES

Recent studies in humans have demonstrated that immedi-
ately after a single bout of exercise, there are profound changes
in the mechanisms that regulate and determine arterial pressure.
These changes result in a post-exercise hypotension that lasts
nearly 2 h in healthy individuals and may last beyond 12 h in
hypertensive patients (9). Several reviews have documented
many aspects of post-exercise hypotension, including early ob-
servations of post-exercise hypotension and the evidence that
post-exercise hypotension is also observed in animal models
(3,9,14). The primary purpose of this review is to integrate
selected recent findings, from human and animal studies, that
have contributed to either an enhanced understanding of the
mechanisms or an appreciation of the potential clinical rele-
vance of post-exercise hypotension. Recent work suggests that
the cause of post-exercise hypotension is two-fold, involving
both neural and local mechanisms (5,6). The clinical implica-
tions of post-exercise hypotension are only now being investi-
gated in prospective studies, but post-exercise hypotension may
contribute to some of the long-term adaptations associated with
exercise training, such as amelioration of hypertension and
plasma volume expansion.
Address for correspondence: John R. Halliwill, Ph.D., SMH 4 –184 W. Joseph, Mayo
Clinic and Foundation, 200 First Street SW, Rochester, MN 55905 (E-mail:
halliwill.john@mayo.edu).
Accepted for publication: January 4, 2001.
0091-6631/2902/65–70
Exercise and Sport Sciences Reviews
Copyright © 2001 by the American College of Sports Medicine
Numerous studies have confirmed the existence of post-
exercise hypotension in normotensive and hypertensive in-
dividuals as well as in several animal models (e.g., spontane-
ously hypertensive rats) (9). In young healthy normotensive
individuals, moderate-intensity dynamic exercise for 30 – 60
min will produce post-exercise blood pressure reductions on
the order of 5–10 mm Hg in the supine position that last
several hours. Typically, post-exercise hypotension is more
apparent in hypertensive individuals, reaching 20 mm Hg
and lasting up to 12 h (4,9). The magnitude of pressure
reductions is exaggerated in the seated or standing positions
(9).
In comparison with rest (e.g., pre-exercise), post-exercise
hypotension is characterized by a persistent drop in systemic
vascular resistance that is not completely offset by increases
in cardiac output (5–7,9). On a simplistic level, this hemo-
dynamic state can be seen as a transition between that
occurring during large-muscle dynamic exercise and that of
the resting state. With the termination of exercise, cardiac
output declines from high exercising values more rapidly
than systemic vascular resistance recovers. This imbalance in
the two determinants of arterial pressure results in a hypo-
tension that is maintained for hours. Several other aspects of
the post-exercise hemodynamic state merit comments.
First, forearm and calf vascular resistance decreased in
parallel with systemic vascular resistance by ~ 30% (5–7,9).
Thus, the vasodilation that underlies post-exercise hypoten-
sion is not restricted to the sites of active skeletal muscles
(i.e., the legs) but instead involves inactive regions as well
(e.g., the arms). Second, the associated rise in arterial blood

65

Earlier tenets that now appear to be incorrect in humans
Earlier tenet
Post-exercise hypotension is caused by endogenous opioids.
Post-exercise hypotension is mediated by sympathoinhibition.
Nitric oxide is the major vasodilator substance that is involved.
inflow through the vasodilated regions contributes to an
increase in venous pooling of blood. During exercise, the
rhythmically contracting skeletal muscles in the leg reduce
the degree of venous pooling by squeezing veins, in effect,
pumping blood back to the heart. This “muscle pump” ac-
tivity is absent during passive recovery from exercise. Third,
the increase in venous pooling, in conjunction with the loss
of plasma volume associated with exercise, leads to a reduc-
tion in central venous pressure (~ 2 mm Hg supine) and
cardiac filling pressure (preload) (6). Fourth, despite this fall
in cardiac preload, stroke volume is maintained due to the
reduction in cardiac afterload and a probable increase in
cardiac contractility (5,6). The net result of these influences
on the blood vessels and heart is that cardiac output is
elevated (heart rate is higher and stroke volume is unchanged
compared with before exercise). Thus, it is generally accepted
that in most persons, post-exercise hypotension is due to a
persistent drop in systemic vascular resistance that is not
completely offset by increases in cardiac output.
FACTORS THAT INFLUENCE POST-EXERCISE
HYPOTENSION
Several factors have been identified either anecdotally or
in prospective studies that can modify the magnitude or
duration of post-exercise hypotension.
Exercise Modality, Duration, and Intensity
Post-exercise hypotension can be observed after several
modes of large muscle mass dynamic exercise (e.g., cycling or
running) (9). Although shorter or less vigorous exercise
protocols elicit inconsistent changes in arterial pressure in
normotensive individuals, post-exercise hypotension is con-
sistently elicited after longer (30 – 60 min) bouts of moderate-
intensity (50 – 60% V̇O2peak) exercise. Shorter (⬍ 30 min)
and less intense bouts of exercise may readily produce post-
exercise hypotension in hypertensive patients but not in
normotensive individuals. It is unknown what effect exercise
training has on these “dose-response” relationships to
exercise.
Environmental Factors
Many of the environmental factors that have an impact on
post-exercise hypotension can be predicted by understanding
the fundamental hemodynamic changes outlined in Figure 1.
It is expected that exercise in a hot environment will exac-
erbate post-exercise hypotension in two ways: a greater loss of
plasma volume due to sweating and a greater drop in vascular
resistance due to vasodilation of the cutaneous circulation. In
66 Exercise and Sport Sciences Reviews
TABLE 1
New understanding
Role of opioids appears to be negligible in humans.
Role of sympathoinhibition may be limited; vasodilator substances may play a
major role.
Role of nitric oxide may be limited; other vasodilator substances are likely
involved.
contrast, fluid replacement may lessen post-exercise hypo-
tension (2). Active recovery, by maintaining action of the
muscle pump, would likely reduce post-exercise hypotension
compared with passive recovery, but this has not been studied
systematically. Orthostasis (e.g., seated upright or standing
recovery from exercise) positions the major vasodilated vas-
cular beds below heart level and exaggerates the magnitude of
venous pooling. This could further reduce central venous
pressure, cause cardiac output to fall, and result in reduced
orthostatic tolerance.
Population Differences
Post-exercise hypotension has been observed in numerous
populations, including young and older normotensive men
Figure 1. Schematic overview of hemodynamic changes during post-
exercise hypotension in comparison with the resting state. A. Systemic
vascular resistance is decreased by ~ 30%. B. The associated rise in blood
flow through the vasodilated regions contributes to an increase in venous
pooling of blood. C. The “muscle pump” that reduces the degree of
venous pooling during exercise is absent during passive recovery from
exercise. D. The increase in venous pooling, in conjunction with the loss of
plasma volume associated with exercise, leads to a reduction in central
venous pressure (~ 2 mm Hg supine) and cardiac filling pressure (preload).
E. Despite this fall in cardiac preload, stroke volume is maintained due to
the reduction in cardiac afterload and a probable increase in cardiac
contractility. The net result of these influences on the blood vessels and
heart is that cardiac output is elevated. Thus, post-exercise hypotension (F)
results from a sustained drop in vascular resistance that is not completely
offset by a rise in cardiac output. LA, left atrium; LV, left ventricle; RA, right
atrium; RV, right ventricle.
www.acsm-essr.org
and women, borderline or established hypertension, and nor-
motensive African Americans. In most of these populations,
the hemodynamic response is quantitatively analogous to
that shown in Figure 1 (e.g., in hypertension, the amplitude
and duration of responses are exaggerated relative to normo-
tensive controls). However, in older (⬎ 60 y old) hyperten-
sive patients, the hemodynamics underlying post-exercise
hypotension may be divergent from that of other population
groups. Hagberg and co-workers (4) found that post-exercise
hypotension was mediated by a decrease in cardiac output
(systemic vascular resistance was elevated) in older hyper-
tensive patients. The fundamental cause appeared to be a
decrease in stroke volume that was attributed to either re-
duced venous return or reduced myocardial contractility. It
should be noted that this group of subjects was studied during
recovery in a seated position. Thus, this apparent discrepancy
in results may be related to interactions among aging, hyper-
tension, and the superimposed orthostatic stress (seated re-
covery). Again, the general view is that post-exercise hypo-
tension arises from a reduction in systemic vascular resistance
and not from a fall in cardiac output, but exceptions have
been found. These exceptions warrant further study.

MECHANISMS OF POST-EXERCISE HYPOTENSION

Recent research has focused on the mechanisms responsi-
ble for the sustained decrease in regional and systemic vas-
cular resistances after a single bout of exercise. Findings
indicate that this sustained vasodilation is associated with
two alterations in sympathetic vascular regulation: what has
been defined as a “neural” and a “vascular” component (5)
(as shown in Figure 2). The neural component of this vaso-
dilation is a reduction on the order of ~ 30% in the outflow
of sympathetic vasoconstrictor nerve activity to skeletal mus-
cle vascular beds (5,7,9). The vascular component refers to
the attenuation of vascular responses to sympathetic vaso-
constriction, as well as the potential influence of local and
circulating vasodilator substances.
Sympathoinhibition After Exercise
Multiple studies have documented that the amount of
activity in the sympathetic nerve fibers that control vaso-
constriction in the leg is inhibited during post-exercise hy-
potension in humans (5,7,9) and in some animal models
(10). Under resting conditions, muscle sympathetic nerve
activity is under strong regulation by the arterial baroreflexes
and cardiopulmonary receptor reflexes. During exercise, the
baroreflex is “reset” to a higher operating point and sympa-
thetic activity is increased. After exercise, these reflexes are
reset to lower pressures such that sympathetic outflow from
the central nervous system is lower than pre-exercise levels
(3,5). Early studies in animals suggested that this sympa-
thoinhibition might be the result of activation of endogenous
opioid receptor pathways in the central nervous system (14).
Although this was a popular notion, it does not appear to be
the case during post-exercise hypotension, in that the block-
ade of opioid receptors with naloxone does not alter post-
exercise sympathetic nerve activity or arterial pressure in
humans (7), and the more recent research on this mechanism
Figure 2. Schematic overview of changes in neural control of the cir-
culation related to post-exercise hypotension. The sustained drop in vas-
cular resistance that underlies post-exercise hypotension has both a “neu-
ral” and a “vascular” component. Arterial baroreflexes are reset to
maintain lower arterial pressure such that sympathetic vasoconstrictor
nerve activity is less for a given pressure. Likewise, vascular responsiveness
to sympathetic nerve activity is blunted, leading to less vascular resistance
for a given level of nerve activity. Finally, it appears that vasodilator sub-
stances produce a further drop in vascular resistance. All of these factors
contribute to the reduction in arterial pressure.
in animals has had inconsistent results (13). The central
nervous system mechanisms involved in baroreflex resetting
during exercise and post-exercise hypotension are unknown.
Vasodilator Substances
In addition to reductions in sympathetic outflow, vascular
responsiveness to ␣-adrenergic receptor stimulation is im-
paired so that vascular resistance is reduced for a given level
of nerve activity after exercise (3,5,12). The nature of this
vascular component of post-exercise hypotension is un-
known, but ineffective transduction of sympathetic outflow
into vascular resistance could be the result of competing
influences at the level of the arterial smooth muscle, such as
the release of local vasodilator substances, or by modulation
of the ␣-adrenergic pathway (e.g., either presynaptic or
postsynaptic inhibition).
Factors associated with acute exercise, such as increases
in blood flow, cyclic wall stress associated with pulsatile
blood flow, and catecholamines, stimulate the release of
nitric oxide from the vascular endothelium. In fact, studies
in humans have suggested that nitric oxide production
may be increased after acute exercise (11). It is also well
established that nitric oxide attenuates the vasoconstrictor
response to ␣-adrenergic receptor stimulation. Along
these lines, evidence in animal models (3,12) suggests that

Volume 29 䡠 Number 2 䡠 April 2001 Post-exercise Hypotension in Humans 67


nitric oxide contributes to post-exercise hypotension by
blunting vasoconstrictor responses. However, there are a
number of other potential vasodilators that could poten-
tially modify ␣-adrenergic responsiveness, as illustrated in
Figure 3.
Recent Observations
Two recent studies attempted to address the importance of
neural (sympathoinhibition) and vascular (vasodilator sub-
stances) effects in mediating post-exercise hypotension. First,
a study by VanNess et al. (15) used a ganglionic receptor
antagonist to block sympathetic outflow in rats. This inter-
vention resulted in a ⬎ 85% reduction in post-exercise
hypotension (from ⫺9 to ⫺1 mm Hg). In contrast, a study by
Halliwill et al. (6) used an infusion of an ␣-adrenergic an-
tagonist to block sympathetically mediated vasoconstriction
in normotensive humans. This intervention did not alter
post-exercise hypotension (Figure 4), although it appeared
that ~ 30% of the drop in systemic vascular resistance could
be attributed to loss of sympathetic vasoconstriction after
exercise. The authors were unable to attribute any of the
reductions in regional vascular resistance or arterial pressure
to changes in sympathetic vasoconstriction. These results are
perplexing and suggest that the role of sympathoinhibition in
causing post-exercise hypotension is both complex and lim-
ited in normotensive humans. It is possible that the role of
sympathoinhibition is more pronounced in patients with
elevated levels of sympathetic activity (e.g., primary
hypertension).
Recent work has also investigated the role of nitric oxide–
mediated vasodilation after exercise. Halliwill et al. (6)
tested the extent to which, in normotensive humans, sys-
temic nitric oxide synthase inhibition can reverse post-exer-
cise hypotension. They found that arterial pressure continues
to be lower after exercise compared with a control day, even
after the blockade of nitric oxide production (Figure 4).
Thus, in contrast to animal studies, it does not appear that
post-exercise hypotension is dependent on increased produc-
tion of nitric oxide in normotensive humans. It must be
68 Exercise and Sport Sciences Reviews
Figure 3. Schematic overview of
neural and local control of vascular
tone related to post-exercise hypo-
tension. During post-exercise hypo-
tension, diminished vasoconstrictor
responses and vasodilation may be
produced by a host of potential vaso-
dilator substances acting via presyn-
aptic (A) or postsynaptic (B) modula-
tion of the ␣-adrenergic pathway or
by direct effects on smooth muscle
relaxation (C).
noted that in this study, nitric oxide synthase inhibition was
performed after ␣-adrenergic receptor blockade, to isolate the
effects of humoral dilators from ongoing neural changes. As
such, this study cannot exclude a role for nitric oxide in
modifying ␣-adrenergic responses after exercise.
In this context, it is becoming evident that sympathoin-
hibition and changes in nitric oxide production cannot ac-
count for all of the vasodilation after exercise. It seems likely
that some factor or factors are released by the exercised
muscle (e.g., adenosine, prostaglandins) and continue to re-
duce vascular tone for an extended period of time after
exercise ceases. Unfortunately, the identity of a single such
substance is likely to remain elusive, and multiple substances
may be involved. In summary, many of the earlier tenets
regarding post-exercise hypotension in humans are being
rewritten as our understanding of the phenomenon advances.
A future area of research will be extending this understanding
to why post-exercise hypotension is more pronounced in
individuals with hypertension (i.e., what mechanism or
mechanisms are augmented in that state?).
CLINICAL IMPLICATIONS OF POST-EXERCISE
HYPOTENSION
Neither the physiological nor the pathophysiological con-
sequences of post-exercise hypotension have been studied
systematically, despite the demonstration of alterations in
cardiovascular regulation after exercise. However, several
important observations hint at the clinical significance of
post-exercise hypotension.
Orthostatic Hypotension and Syncope
From the changes outlined in Figure 1, it can be inferred
that post-exercise hypotension has many characteristics that
would contribute to orthostatic hypotension and predispose
toward syncope. The ability to defend against orthostatic
stress is compromised by enhanced venous pooling, reduced
venous return, and reduced sympathetic outflow. Further-
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Figure 4. Data on systemic hemodynamics during recovery from exer-
cise (Exercise day; filled columns) compared with recovery from seated rest
(Control day; open columns) under three conditions: (1) without block-
ade, (2) after systemic blockade of ␣-adrenergic receptors, and (3) after
␣-adrenergic blockade combined with systemic inhibition of nitric oxide
synthase (note that the scale of the y-axis is different for this last condition
in both graphs). Arterial pressure remained lower after exercise compared
with the control day under all conditions. (Modified with permission from
Halliwill, J.R., C.T. Minson, and M.J. Joyner. Effect of systemic nitric oxide
synthase inhibition on postexercise hypotension in humans. J. Appl.
Physiol. 89:1830 –1836, 2000.)
more, the baroreflexes are reset to defend pressure at a lower
level (6). Thus, orthostatic tolerance is often reduced in
healthy individuals during the first hours after exercise, and
syncopal episodes are not uncommon immediately after ex-
ercise. Studies have not identified what factors might influ-
ence the incidence of orthostatic intolerance after exercise or
determined the extent to which post-exercise hypotension in
the supine position would predict orthostatic intolerance
after exercise.
Long-Term Adaptations and Hypertension
Hypertension is a major health issue in the United States.
One in four adults in the United States (~ 50 million indi-
viduals) have hypertension. Thus, development and under-
standing of nonpharmacological treatment modalities for hy-
pertension continue to deserve high priority. Along these
lines, aerobic exercise has come to the forefront of nonphar-
macological treatments for hypertension. The antihyperten-
sive effects of aerobic exercise are poorly understood, but it is
likely that the mechanisms that play a role in mediating
Volume 29 䡠 Number 2 䡠 April 2001
post-exercise hypotension are linked to long-term adapta-
tions that occur during exercise training and, thus, are im-
portant to understand. The extent to which the pressure-
lowering effects of exercise training reflect the integration or
carryover of the acute effects of exercise (i.e., post-exercise
hypotension) remains unknown. To date, definitive studies
linking post-exercise hypotension to the long-term antihy-
pertensive adaptations associated with exercise training have
yet to be conducted. Of note, several studies by Cléroux and
co-workers have shown the effects of antihypertensive med-
ications are often additive with post-exercise hypotension
(1).
Changes in Fluid Balance
It is intriguing to speculate that post-exercise hypotension
may serve some homeostatic purpose. One such purpose may
be the newly identified role that post-exercise hypotension
appears to play in the recovery of plasma volume after exer-
cise. In a recent study by Hayes et al. (8), a phenylephrine
(␣-adrenergic agonist) infusion was used to prevent post-
exercise hypotension during the first 90 min after exercise.
When compared with a control day on which post-exercise
hypotension was allowed to occur, the normal recovery of
plasma volume was prevented by ⬎ 50% when post-exercise
hypotension was blocked. It is believed that increased plasma
albumin contributes to the plasma volume recovery and
subsequent volume expansion after exercise, and this mech-
anism may be linked to post-exercise hypotension by the
pressure-dependent transcapillary escape rate of albumin. In
other words, when pressure is lower (i.e., during post-exercise
hypotension), more albumin stays in the intravascular space
and more fluid is drawn into that space from the extravas-
cular space. It remains to be seen whether post-exercise
hypotension has a similar facilitative effect on the plasma
volume expansion that occurs 24 h after a single bout of
exercise.
SUMMARY
A review of the evidence indicates that post-exercise hy-
potension is common after moderate-intensity dynamic ex-
ercise in both normotensive and hypertensive individuals
and that hemodynamic responses are greater in hypertensive
patients. The hypotension results from persistent reductions
in vascular resistance, mediated by the autonomic nervous
system and vasodilator substances. Post-exercise hypotension
may play an important role in recovery of plasma volume
after exercise and may be linked to long-term adaptations to
exercise training.
Acknowledgments
I thank Dr. Michael J. Joyner for comments on the manuscript. This research
was supported in part by a grant from the American Heart Association,
Northland Affiliate, Inc. (Scientist Development Grant 30403Z).
Post-exercise Hypotension in Humans 69
References
1. Beaulieu, M., A. Nadeau, Y. Lacourciére, and J. Cléroux. Post-exercise
reduction in blood pressure in hypertensive subjects: effects of angio-
tensin converting enzyme inhibition. Br. J. Clin. Pharmacol. 36:331–
338, 1993.
2. Davis, J.E., and S.M. Fortney. Effect of fluid ingestion on orthostatic
responses following acute exercise. Int. J. Sports Med. 18:174 –178, 1997.
3. DiCarlo, S.E., H.L. Collins, M.G. Howard, C.-Y. Chen, T.J. Scislo, and
R.D. Patil. Postexertional hypotension: a brief review. Sports Med.
Training Rehab. 5:17–27, 1994.
4. Hagberg, J.M., S.J. Montain, and W.H. Martin. Blood pressure and
hemodynamic responses after exercise in older hypertensives. J. Appl.
Physiol. 63:270 –276, 1987.
5. Halliwill, J.R., J.A. Taylor, and D.L. Eckberg. Impaired sympathetic
vascular regulation in humans after acute dynamic exercise. J. Physiol.
(Lond. ) 495:279 –288, 1996.
6. Halliwill, J.R., C.T. Minson, and M.J. Joyner. Effect of systemic nitric
oxide synthase inhibition on postexercise hypotension in humans.
J. Appl. Physiol. 89:1830 –1836, 2000.
7. Hara, K., and J.S. Floras. Effects of naloxone on hemodynamics and sym-
pathetic activity after exercise. J. Appl. Physiol. 73:2028–2035, 1992.
70 Exercise and Sport Sciences Reviews
8. Hayes, P.M., J.C. Lucas, and X. Shi. Importance of post-exercise hypoten-
sion in plasma volume restoration. Acta Physiol. Scand. 169:115–124, 2000.
9. Kenny, M.J., and D.R. Seals. Postexercise hypotension: key features,
mechanisms, and clinical significance. Hypertension 22:653– 664, 1993.
10. Kulics, J.M., H.L. Collins, and S.E. DiCarlo. Postexercise hypotension is
mediated by reductions in sympathetic nerve activity. Am. J. Physiol.
276:H27–H32, 1999.
11. Jungersten, L., A. Ambring, B. Wall, and Å. Wennmalm. Both physical
fitness and acute exercise regulate nitric oxide formation in healthy
humans. J. Appl. Physiol. 83:760 –764, 1997.
12. Patil, R.D., S.E. DiCarlo, and H.L. Collins. Acute exercise enhances
nitric oxide modulation of vascular response to phenylephrine. Am. J.
Physiol. 265:H1184 –H1188, 1993.
13. Sebastian, L.A., M.M. Moran, and C.M. Tipton. Post-exercise hypo-
tension and intra-cerebroventricular (ICV) injections of ␤-endorphin
and naloxone hydrochloride. FASEB J. 9:A361, 1995. (Abstract).
14. Thorén, P., J.S. Floras, P. Hoffman, and D.R. Seals. Endorphins and
exercise: physiological mechanisms and clinical implications. Med. Sci.
Sports Exerc. 22:417– 428, 1990.
15. VanNess, J.M., H.J. Takata, and J.M. Overton. Attenuated blood pres-
sure responsiveness during post-exercise hypotension. Clin. Exp. Hyper-
tens. 18:891–900, 1996.
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