(Hypertension. 1995;26:676-683.)
© 1995 American Heart Association, Inc.
Articles |
Acute Exercise Attenuates Cardiac Autonomic Regulation in Hypertensive Rats
From the Department of Physiology, Northeastern Ohio Universities, College of Medicine, Rootstown.
Correspondence to Stephen E. DiCarlo, PhD, Department of Physiology, Northeastern Ohio Universities, College of Medicine, PO Box 95, Rootstown, OH 44272. E-mail sdicarlo@riker.neoucom.edu.
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Abstract |
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Abstract Dynamic exercise may be used as a safe, therapeutic approach to reduce sympathetic nerve activity at rest and thus may be beneficial for individuals with hypertension. Therefore, we tested the hypothesis that a single bout of mild to moderate dynamic exercise would decrease cardiac sympathetic tonus at rest. We designed two experimental protocols to test this hypothesis in male spontaneously hypertensive rats. In protocol 1 (n=6) cardiac sympathetic tonus and parasympathetic tonus were determined before and after a single bout of dynamic exercise. We developed protocol 2 (n=5) to determine the component of the autonomic nervous system responsible for the postexercise reduction in heart rate. Rats were instrumented with catheters inserted into the descending aorta for measurements of arterial pressure, mean arterial pressure, and heart rate and into the jugular vein for infusion of drugs. A single bout of mild to moderate dynamic treadmill exercise (12 m/min, 10% grade for 42±1 minutes, representing approximately 74% to 79% of maximal heart rate) resulted in a postexercise reduction in mean arterial pressure (163±7 to 149±5 mm Hg; P<.05). Associated with the postexercise hypotension was a reduction in sympathetic and parasympathetic tonus (47±12% and 71±12%, respectively). The reduction in heart rate during the early recovery phase was due to a withdrawal of sympathetic tonus, because ß1-adrenergic receptor blockade significantly enhanced the postexercise reduction in heart rate, and muscarinic-cholinergic receptor blockade did not affect the postexercise decrease in heart rate until 20 minutes after exercise. These results demonstrate that (1) sympathetic tonus and parasympathetic tonus are attenuated after a single bout of dynamic exercise and (2) the reduction in sympathetic tonus and parasympathetic tonus mediated cardiodeceleration during the early recovery period.
Key Words: blood pressure • exercise • heart rate • hypertension, genetic • autonomic nervous system
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Introduction |
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A reduction in AP after a single bout of dynamic exercise (PEH) has been documented in normotensive1 2 and hypertensive3 4 individuals and SHR.5 6 BP is reduced more2 7 and PEH persists longer8 in hypertensive individuals and animals. It has been reported that even brief (10 minutes) exercise can result in a reduction in BP in hypertensive subjects.9 Inhibition of SNA is one of the proposed mechanisms for PEH.9 10 11 This sympathoinhibition may be beneficial for individuals with hypertension or other cardiovascular disorders in terms of lowering resting BP12 13 and preventing cardiac arrhythmia.14 Therefore, attention has been focused on postexercise inhibition of SNA in individuals with hypertension. For example, Floras et al9 recorded postganglionic MSNA directly from the peroneal nerve of individuals with borderline hypertension and reported a 42% reduction in MSNA 60 minutes after a single bout of exercise. Similarly, a decrease in AP and SNA has been reported after stimulation of the sciatic nerve (simulated exercise) in hypertensive rats.7 8
In contrast, in normotensive individuals Hara and Floras15 found that MSNA and plasma norepinephrine levels remained unchanged from control levels in the presence of PEH. Similarly, Floras and Senn16 reported no decreases in AP or MSNA in normotensive individuals after a bout of dynamic exercise. These results suggest that the reduction in SNA may be modulated by the resting level of AP.
Additional experimental evidence suggests that a single bout of dynamic exercise alters the regulation of sympathetic activity in individuals with hypertension. For example, tachycardia would be anticipated in response to the decrease in BP after exercise. Although three studies have reported a postexercise tachycardia in the presence of PEH,17 18 19 two of these studies examined the postexercise responses to maximal exercise in normotensive subjects.18 19 Only Cléroux et al17 reported a significant tachycardia after submaximal exercise in hypertensive subjects. In contrast, after mild to moderate exercise in hypertensive humans3 and animals,5 HR was unchanged in the presence of PEH. Floras et al9 proposed that the absence of a reflex tachycardia in response to PEH might be due to altered neural regulatory mechanisms. This may result from a decreased intrinsic HR, an attenuated cardiac ST, and/or an enhanced cardiac PT. Cardiac ST and PT are defined as the independent influences of sympathetic and parasympathetic efferent effects on HR.
The purpose of the present study was to test the hypothesis that a single bout of dynamic exercise alters cardiac ST. This purpose was achieved by determining cardiac ST and PT in SHR before and, on alternate days, after a single bout of dynamic exercise.
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Methods |
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Design
We designed this study to examine the effects of a single bout of dynamic exercise on the autonomic control of HR. Specifically, we tested the hypothesis that a single bout of dynamic exercise reduces the influence of the sympathetic nervous system on HR. Experiments were conducted in male SHR (n=6, 12 to 15 weeks old, 326±7 g). AP, MAP, and HR were recorded before, during, and after exercise under two experimental protocols.
In protocol 1 (n=6, autonomic tonus) we determined cardiac ST and PT before and after a single bout of dynamic exercise. Two experimental trials were required for determination of cardiac ST and PT before and after exercise. In protocol 2 (n=5, autonomic influence) we determined the limb of the autonomic nervous system (sympathetic and/or parasympathetic) responsible for the postexercise reduction in HR. Two experimental trials were also required for determination of the autonomic component contributing to the postexercise reduction in HR. All procedures were performed in accordance with guidelines established by the institutional animal care and use committee.
Surgical Procedures
All instrumentation was performed with the use of aseptic
surgical procedures. Anesthesia was obtained with sodium
pentobarbital (40 mg/kg IP), and supplemental doses were administered
as needed. Rats were instrumented with a
polytetrafluoroethylene catheter inserted
into the descending aorta via the left common carotid artery for
measurements of AP, MAP, and HR and a Tygon catheter in the jugular
vein for infusion of cardiac autonomic antagonists.
Catheters were flushed every other day, filled with heparin (1000
U/mL), and plugged with paraffin-filled obturators. Rats were
monitored for signs of infection and weighed daily. The rats were
allowed to recover for 4 to 5 days before experimentation. During this
time the rats were brought to the laboratory daily and familiarized
with the treadmill and experimental procedures. At the time of the
experimental protocols all the rats had recovered, were healthy, and
were gaining weight.
AP was determined by connecting the arterial catheter to a Gould P23XL pressure transducer coupled to a Gould RS3600 physiograph. MAP was derived electronically with a low-pass filter. HR was determined with a Gould electrocardiograph/Biotach model 20-4615-65 that was triggered from the AP pulse. All data were displayed on the physiograph and were sampled by a data acquisition system and laboratory computer (MacLab 8 analog-to-digital convertor, Analog Digital Instruments Pty Ltd, and LCII Macintosh computer) for subsequent analysis.
Experimental Protocol 1 (Autonomic Tonus)
Cardiac ST and PT were determined before and after a single bout
of dynamic exercise. Determination of ST and PT required two
experimental trials, each separated by more than 48 hours. Thus, each
rat was studied twice before and twice after exercise.
For experimental trial 1 rats were placed unrestrained in a large Plexiglas box (30.5x30.5x30.5 cm). The rats were allowed to adapt to the laboratory environment for 1 hour so baseline hemodynamic variables could be obtained. After the adaptation period the HR, AP, and MAP responses to ß1-adrenergic and muscarinic-cholinergic receptor blockades were determined. Cardiac muscarinic-cholinergic receptor blockade was achieved by injection of the nonspecific muscarinic-cholinergic receptor antagonist methylatropine (10 mg/kg) through the jugular venous catheter. Because the HR response to methylatropine reaches its peak in 10 to 15 minutes,20 this time interval was standardized before the HR measurement. Cardiac ß1-adrenergic receptor blockade was achieved by injection of the specific ß1-adrenergic receptor antagonist metoprolol (10 mg/kg) into the jugular venous catheter. Metoprolol was infused 15 minutes after methylatropine, and again the HR response was measured after 15 minutes. The entire data collection took approximately 2 hours. At the end of the experiment the rats were returned to their housing facilities. On an alternate day (>48 hours) experimental trial 2 was conducted. Rats were treated identically as described for experimental trial 1 except the order of blockade was reversed. Intrinsic HR (HRI) was considered to be HR after complete cardiac autonomic efferent blockade (muscarinic-cholinergic and ß1-adrenergic receptor blockades). ST was calculated as HRM-HRI, and PT as HRB-HRI, where HRM is HR after muscarinic-cholinergic receptor blockade and HRB is HR after ß1-adrenergic receptor blockade.
Experimental trials 1 and 2 were repeated after a single bout of dynamic exercise. The procedures were identical to those described above except that the adaptation time was replaced by a single bout of treadmill running. Each rat ran on a motor-driven treadmill at 12 m/min, 10% grade, for 42±1 minutes. Twenty minutes after the exercise selective cardiac autonomic blockade was performed as described above. ß1-Adrenergic and muscarinic-cholinergic receptor blocking agents were administered 20 minutes after exercise in an effort to study autonomic tonus at a time when PEH would most likely be present. As previously reported by Overton and colleagues5 PEH was evident in SHR as early as 20 minutes after exercise and continued through 60 minutes of recovery. All measures of autonomic tonus were made during this steady-state period.
Experimental Protocol 2 (Autonomic Influence)
We were surprised to determine that a single bout of dynamic
exercise significantly reduced both ST and PT. To confirm these results
we determined the effect of ß1-adrenergic and
muscarinic-cholinergic receptor blockades on the reduction of HR
after exercise. This protocol, which also required two experimental
trials, determined the component of the autonomic nervous system that
mediates the reduction in HR after exercise.
For experimental trial 1 rats were placed unrestrained on the treadmill and allowed to adapt for 1 hour. After the adaptation period each rat ran on a motor-driven treadmill as described for protocol 1. Approximately 5 minutes before completing the exercise, the rats were treated with either metoprolol or methylatropine and monitored for the remaining period of exercise and for a period of 20 minutes after exercise. For experimental trial 2 the alternate antagonist was administered. The order of drug administration was randomized for this protocol as well.
The effectiveness of the muscarinic-cholinergic and ß1-adrenergic receptor blockades (determined at the completion of the protocol) was evaluated by the change in HR in response to changes in AP produced by intravenous infusion of phenylephrine hydrochloride (1.5 µg/kg) and nitroglycerin (0.15 mg/kg) (Fig 1).
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Drugs
Methylatropine and metoprolol were purchased from Sigma Chemical
Co. Phenylephrine hydrochloride was purchased from
Winthrop-Breon and nitroglycerin from Lyphomed.
Data Analysis
All data are expressed as mean±SEM. MAP responses before,
during, and after exercise during the two trials of protocol 1 and the
two trials of protocol 2 were not significantly different; therefore,
they were averaged within protocols and are presented
separately in Fig 2A and 2B. A one-way ANOVA with
repeated measures was used to evaluate MAP before, during, and after
exercise (Fig 2). Differences observed were further
evaluated with Fisher's least significant difference post hoc test.
Similarly, HR responses before, during, and after exercise during the
two trials in protocol 1 were averaged and are presented in Fig 3. Resting and intrinsic HR values were averaged between
trials and within both protocols. Differences were tested for
significance with paired t tests. Differences in ST and PT
between the no-exercise and postexercise conditions were tested for
significance with paired t tests (Fig 4). The
overall differences in HR responses among protocol 1 and the two trials
from protocol 2 were tested for significance with a two-way ANOVA
with repeated measures across time. When significant differences were
observed, further intergroup multiple comparisons at various times were
made with Fisher's least significant difference post hoc test (Fig 5).
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Results |
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Effect of Drugs on MAP and HR
The interpretation of and conclusions from our results depend on the effectiveness of the blockade produced by the autonomic antagonists metoprolol and methylatropine. Fig 1 is an analog recording that demonstrates the effectiveness of muscarinic-cholinergic and ß1-adrenergic receptor blockades. This figure illustrates the HR response to changes in AP produced by intravenous infusion of phenylephrine hydrochloride (1.5 µg/kg) and nitroglycerin (0.15 mg/kg). Phenylephrine produced a 34±6 mm Hg increase in MAP, with a decrease in HR of 8±3 bpm. Nitroglycerin (0.15 mg/kg) produced a 35±6 mm Hg decrease in MAP, with a paradoxical decrease in HR of 3±3 bpm.
Table 1 presents the MAP and HR responses before and after cardiac autonomic blockade in the no-exercise and postexercise conditions. Cardiac autonomic blockade did not significantly change MAP in any of the conditions. This is an important consideration because changes in pressure may have reflexly altered HR. Under the no-exercise condition, both muscarinic-cholinergic and ß1-adrenergic receptor blockades significantly changed HR in the two trials (P<.05). However, after exercise muscarinic-cholinergic receptor blockade did not significantly change HR in either trial (P>.05).
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Table 2 presents MAP values 5 minutes before the cessation of exercise (-5 minutes), at the cessation of exercise (0 minutes), and during 20 minutes of recovery for the no-blockade condition in protocol 1 and after selective muscarinic-cholinergic and ß1-adrenergic receptor blockades in protocol 2. Although MAP decreased after both ß1-adrenergic and muscarinic-cholinergic receptor blockades, BP did not differ significantly after blockade between the two conditions or from the no-blockade condition. These results illustrate that blockade of one limb of the autonomic nervous system did not reflexly alter the other limb by changes in AP. These findings confirm the results of protocol 1.
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Effect of Exercise on MAP and HR
MAP before, during, and after exercise for protocol 1 was
determined during two experimental trials. MAP responses between trials
did not differ significantly (P>.05); therefore, MAP
responses were averaged and are presented in Fig 2. During protocol 1 (Fig 2A) MAP
increased significantly from 163±7 mm Hg (0 minutes) before
exercise to 180±7 mm Hg 10 minutes after treadmill exercise was
started (P<.05). At 40 minutes of exercise MAP was 173±5
mm Hg. MAP significantly decreased to 149±5 mm Hg 20 minutes after
exercise (P<.05). Thus, MAP was decreased by 14±4 mm Hg
20 minutes after exercise compared with the preexercise value. Similar
changes were observed during protocol 2 (Fig 2B). MAP
increased significantly from 176±5 mm Hg (0 minutes) before exercise
to 186±7 mm Hg 10 minutes after the treadmill exercise was started
(P<.05). MAP significantly decreased to 157±6 mm Hg
(–18±5 mm Hg, P<.05) 20 minutes after exercise. Thus,
mild to moderate dynamic treadmill exercise significantly decreased MAP
during both protocols.
HR before, during, and after exercise for protocol 1 was determined during two experimental trials. The HR response between trials did not differ; therefore, HR responses were averaged and are presented in Fig 3. HR was 322±11 bpm (0 minutes) before exercise and increased significantly (P<.05) to 463±15 bpm 10 minutes after the exercise was started. At 40 minutes of exercise HR was 476±14 bpm. This HR value represents approximately 79% of maximal HR. Twenty minutes after exercise HR decreased to 332±7 bpm. The steady-state HR after exercise was not significantly different from the preexercise HR. Thus, mild to moderate dynamic exercise sufficient to produce PEH did not significantly alter postexercise HR.
Preexercise and Postexercise ST and PT
Fig 4 illustrates ST and PT in the no-exercise
and postexercise conditions in protocol 1. Both ST and PT were
significantly attenuated after exercise. ST and PT significantly
decreased from the no-exercise values of 47±8 and
-41±9 bpm to the postexercise values of 25±6 and -10±3
bpm, respectively. These changes represent a decrease of
47±12% in ST and 71±12% in PT after exercise. These results
demonstrate that a single bout of dynamic exercise significantly
altered the autonomic regulation of HR. Resting HR (323±8 versus
332±7 bpm) and intrinsic HR (325±10 versus 312±7 bpm) did not differ
significantly between the no-exercise and postexercise conditions
(P>.05).
Effect of ß1-Adrenergic and Muscarinic-Cholinergic
Receptor Blockades on HR After Exercise
To assess the contribution of the sympathetic and parasympathetic
components of the autonomic nervous system to HR recovery after
exercise, we compared the cardiodeceleration response to the cessation
of exercise under the three experimental conditions of
ß1-adrenergic receptor blockade,
muscarinic-cholinergic receptor blockade, and no blockade. Fig 5 presents HR values from 5 minutes before the
cessation of exercise (-5 minutes), at the cessation of exercise
(0 minutes), and at 5-minute intervals through 20 minutes of recovery
for protocol 1 and the two experimental trials (after administration of
methylatropine and metoprolol) in protocol 2. Before drug
administration (-5 minutes) HR did not differ significantly
between protocols 1 and 2 (P>.05). In the presence of
ß1-adrenergic receptor blockade HR was significantly
lower than in the no-blockade condition at the cessation of
exercise and at 5, 10, and 15 minutes of recovery. HR did not differ
significantly between the no-blockade and
muscarinic-cholinergic receptor blockade conditions until 20
minutes of recovery. This suggests that the vagal contribution to the
recovery of HR, at least during the early period of recovery, was
undetectable. Taken together, these results suggest that gradual
withdrawal of sympathetic influence was contributing to the rapid drop
in HR during the early period of recovery.
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Discussion |
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Chronic exercise has a significant effect on cardiac autonomic regulatory mechanisms, as demonstrated by a resting bradycardia in trained individuals21 and animals.20 22 However, it is unknown whether a single bout of exercise alters cardiac autonomic regulatory mechanisms. This is of interest because a reduction of cardiac ST may be beneficial for individuals with cardiovascular disorders (ie, hypertension9 or arrhythmia14 ). In the present study a single bout of mild to moderate dynamic exercise sufficient to result in a postexercise reduction in MAP also caused an attenuation of cardiac ST and PT in hypertensive rats. After exercise ST and PT were decreased by 47±12% and 71±12%, respectively, compared with their no-exercise values. Another major finding in this study was that the initial decrease in HR after exercise is mediated by a gradual withdrawal of ST. An increased PT contributes to the reduction in HR 20 minutes after exercise. These results demonstrate that cardiac sympathetic and parasympathetic regulatory mechanisms are attenuated by acute exercise and that postexercise changes in cardiac autonomic control may be involved in the mediation of PEH. For example, factors associated with a single bout of dynamic exercise reduce vascular
1-adrenergic
receptor responsiveness to
catecholamines.23 24 25 26 This suggests that the
vasculature may be less responsive to sympathetic nerve stimulation
after exercise and further suggests that an increased level of
sympathetic activity (increased above preexercise levels) may be
required to maintain AP. However, this study and
others8 9 17 suggest that a single bout of dynamic
exercise sufficient to produce PEH lowers sympathetic activity in
hypertensive populations. These effects of a single bout of exercise
are sustained for less than 48 hours. This is suggested because ST and
PT returned to control values by the time of the second experimental
trial.
ST and PT After Exercise
The postexercise reduction of ST was observed in all six rats.
This result is consistent with studies that have reported a
decreased SNA after exercise in hypertensive populations. For example,
Floras et al9 recorded postganglionic MSNA directly
from the peroneal nerve in individuals with borderline hypertension
before and after exercise. These investigators reported that 45 minutes
of submaximal treadmill exercise, sufficient to produce PEH, lowers
MSNA. These results are supported by animal studies.
Renal7 and mesenteric8 SNA were attenuated
after prolonged stimulation of the sciatic nerve (simulated exercise)
in SHR. Similarly, Anderson and Overton27 reported that
cardiovascular responses to air jet stress were
attenuated after a single bout of exercise in normotensive rats.
However, not all investigators have reported a reduction in SNA after
exercise. For example, Floras et al9 and Hara and
Floras15 reported that normotensive individuals failed to
show decreases in MSNA and/or plasma norepinephrine
concentration after exercise. Therefore, it appears that the
sympathoinhibition may be associated with the resting level of AP.
The decrease in ST may be beneficial for individuals with hypertension. An increase in sympathetic activity and/or responsiveness is associated with the development and maintenance of hypertension.28 29 30 For example, Judy et al29 showed that in SHR both MAP and SNA increased with age and blockade of ganglionic transmission returned AP to normal levels. Similarly, Bunag and Takeda30 reported that increases in sympathetic activity induced by hypothalamic stimulation were always followed by corresponding increases in BP, with larger increases in both BP and SNA in SHR than in normotensive rats. These results demonstrate that an increase in SNA is associated with the development and maintenance of hypertension. Thus, any intervention that decreases SNA, such as mild to moderate dynamic exercise, may contribute to a reduction in AP.
A decrease in ST may also be important in the prevention of cardiac arrhythmias. It has been shown experimentally and clinically that increases in sympathetic activity are involved in the development of ventricular fibrillation, a major cause of cardiac sudden death.14 31 32 33 It has also been demonstrated that a reduction in sympathetic activity by left stellectomy32 (surgical removal of the left stellate ganglion) or exercise training33 is protective against arrhythmias and sudden cardiac death. For example, Schwartz and Stone32 reported that left stellectomy significantly reduced the incidence of ventricular fibrillation in dogs with acute myocardial infarction. Billman et al33 reported that exercise training prevented ventricular fibrillation induced by acute myocardial ischemia. The investigators suggested that left stellectomy and exercise training exert this major protective effect against ventricular fibrillation by reducing the influence of the sympathetic nervous system on the heart. Thus, a decrease in ST, as observed after a single bout of dynamic exercise, may help to prevent cardiac arrhythmias.
All six rats in this study also had a decrease in PT after a single bout of dynamic exercise. Although no studies have reported attenuated PT after a single bout of dynamic exercise in a hypertensive population, three studies have reported attenuated parasympathetic influence in normotensive human subjects. Piepoli et al18 reported reduced vagal tone in normotensive subjects after a maximal cycle ergometer test. Savin et al34 reported a gradual return of parasympathetic activity after a maximal treadmill test in normotensive male subjects. This gradual return of vagal tone through recovery in normotensive subjects was confirmed by Arai et al.35
This is the first study to report this finding in a hypertensive population; however, reductions in PT have been reported after chronic exercise. For example, Negrao et al20 reported a reduction in PT after exercise training in normotensive rats. Similarly, Hassan22 reported a decrease in PT after 6 weeks of exercise training in normotensive rats. Therefore, both chronic and acute exercise attenuate PT. These results lead one to wonder whether the adaptations associated with chronic exercise can be achieved by a single bout of exercise or whether chronic exercise can be considered as consecutive bouts of acute exercise.
A reduced PT after exercise may be important for adequate recovery from exercise by attenuating the reductions in cardiac output and AP. For example, it is generally accepted that there is an excess postexercise oxygen consumption. An elevated cardiac output may be required to facilitate this enhanced oxygen consumption. Since ST is reduced, a corresponding reduction in PT would assure an adequate cardiac output. In fact, cardiac output15 17 and oxygen uptake36 are elevated after a single bout of exercise. In conjunction with the attenuated ST a corresponding decrease in PT may also prevent bradycardia. This is an important consideration because a severe bradycardia during recovery may exacerbate PEH. An enhanced hypotension could result in poor cardiac perfusion and arrhythmias.14 Thus, in the presence of an attenuated ST, a reduction in PT after exercise would be beneficial in maintaining tissue perfusion and allowing adequate recovery from the metabolic demands of the exercise.
Several mechanisms may contribute to the sympathoinhibition after exercise. DiCarlo and colleagues10 proposed that the sympathoinhibition was mediated by a postexercise facilitation of inhibitory cardiopulmonary reflexes. This was proposed because cardiac afferent blockade attenuated the hypotensive effect of a single bout of dynamic exercise,6 and other investigators have shown that the inhibitory influence of cardiac afferents on the circulation may be enhanced after exercise.3 17 Kenney and Seals11 suggested that the sympathoinhibitory effects of a single bout of exercise resulted from sustained somatic afferent stimulation that activates the central endogenous opioid system, leading to sympathoinhibition. Experiments with SHR have suggested that the activation of endogenous opioids during prolonged stimulation of somatic afferents inhibits sympathetic outflow by altering baroreceptor reflexes centrally.7 8 Thus, it seems that the sympathoinhibition evidenced after exercise may result from inhibitory cardiopulmonary afferents and/or inhibitory somatic afferents.
These mechanisms cannot account for the attenuation observed in PT after exercise. However, one contributing factor may be through the actions of neuropeptide Y, a neurotransmitter coreleased with norepinephrine from postganglionic sympathetic nerves. Neuropeptide Y has been shown to inhibit norepinephrine and acetylcholine release from both sympathetic and parasympathetic nerves by a prejunctional mechanism.37 Neuropeptide Y release occurs during sympathetic activation (ie, exercise37 and ischemia38 ). Therefore, an increased release of neuropeptide Y induced by exercise may result in an attenuation in PT and ST.
Depressed ST or PT may also result from desensitization of ß1-adrenergic and muscarinic-cholinergic receptors after exercise.20 39 ST and PT were determined by the differences in HR after differential autonomic blockade; therefore, it is possible that an attenuated sensitivity of ß1-adrenergic and muscarinic-cholinergic receptors is involved in the depressed HR responses to the antagonists.
Factors Mediating the Reduction in HR After Exercise
In protocol 2 we determined the contribution of the sympathetic
and parasympathetic nervous systems to the reduction in HR after a
single bout of dynamic exercise. A priori, we predicted an increase in
PT after exercise. However, having demonstrated an attenuated PT in
protocol 1, we specifically carried out protocol 2 to obtain data that
would either confirm or challenge our results from protocol 1. We
believe that Fig 5 supports the results from protocol 1
demonstrating a reduced PT after exercise. HR during recovery under
ß1-adrenergic receptor blockade was significantly lower
than that during the no-blockade or muscarinic-cholinergic
receptor blockade condition. The first thought was that the lower HR in
this condition must have been due to an unopposed parasympathetic
activity. However, examination of the HR recovery under
muscarinic-cholinergic receptor blockade reveals that there was no
significant difference in the cardiodeceleration from the control
(no-blockade) condition. Thus, the vagal contribution to the
recovery of HR, at least during the early portion of recovery, was
virtually undetectable. These results suggest that a reduction in
cardiac sympathetic activity was the primary mechanism responsible for
the postexercise cardiac slowing. However, the data from the cessation
of exercise (0 minutes) to 5 minutes after exercise (Fig 5) suggest that factors other than the autonomic nervous
system may have contributed to the cardiodeceleration during recovery.
This is suggested because HR continued to decrease from the cessation
of exercise to 5 minutes of recovery when the sympathetic nervous
system was blocked. One potential intrinsic factor contributing to the
postexercise cardiac slowing may be a reduction in cardiac filling
pressure. This is suggested because HR can be increased by the
mechanical stretch associated with increased venous
return.34 Savin and colleagues34 suggested
that the postexercise cardiodeceleration is regulated by alterations in
venous return and thus is an intrinsic property of the intact
circulation. Together with results from the present study these
data suggest that the reduction in HR during the early recovery phase
of exercise is due to reductions in sympathetic activity and intrinsic
properties of the circulation.
One potential limitation of our study is the possibility that blockade of one limb of the autonomic nervous system may have changed the other. We know of two potential reasons that could account for a change in one limb of the autonomic nervous system after blockade of the other limb: a change in AP and "accentuated antagonism."40 If autonomic blockade altered AP, this may have resulted in a reflex change in HR. However, our results showed that MAP did not change significantly after blockade of either limb of the autonomic nervous system in either trial under both the no-exercise and postexercise conditions (Table 1). In addition, Table 2 shows that during protocol 2 the postexercise decrease in MAP was not affected by blockade of either limb of the autonomic nervous system; that is, through recovery, single blockade of ß1-adrenergic or muscarinic-cholinergic receptors did not result in a significant difference in BP between the two conditions or from the no-blockade condition. Thus, we can exclude a change in pressure as a potential reason for a reflex change in the corresponding limb of the autonomic nervous system. However, accentuated antagonism—the concept that one limb of the autonomic nervous system is enhanced when the activity of the other limb is increased—cannot be ruled out. For example, Warner and Russel41 reported that vagal stimulation alone resulted in a decrease in HR from approximately 133 to 60 bpm in dogs. However, in the presence of sympathetic stimulation the same vagal stimulation produced a greater decrease in HR (from 230 to 60 bpm); that is, the effect of vagal stimulation was enhanced when sympathetic output was increased. In addition, it has been reported that bilateral stellate ganglionectomy reduced the magnitude of the HR reduction induced by vagal stimulation in anesthetized cats.42 This suggests that cardiac sympathetic blockade may have reduced the vagal influence on HR. However, although it is possible that reductions in the tone of one limb of the autonomic nervous system after exercise may have reduced the tone in the corresponding limb, there is no documentation of how the basal tone of one limb of the autonomic nervous system changes when the other limb is removed. In addition, our results show that after exercise ST and PT were decreased by 47±12% and 71±12%, respectively. It is unlikely that this large attenuation in ST and PT was due to the effect of the antagonism between the two components of the autonomic nervous system. Thus, within the confines of this limitation we are confident with our findings that a single bout of exercise reduces ST and PT.
In summary, this study demonstrates that ST and PT are attenuated in hypertensive rats after a single bout of dynamic exercise. Our data also suggest that the rate of sympathetic withdrawal mediates the HR reduction during the early recovery phase of exercise. Parasympathetic contribution to the postexercise HR reduction is not evident until the late recovery phase (ie, after 20 minutes). These results indicate that mild to moderate dynamic exercise alters cardiac autonomic regulatory mechanisms.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This study was supported by National Heart, Lung, and Blood Institute grant HL-45245. We wish to thank Heidi L. Collins and Chao-Yin Chen for their skillful technical assistance. We would also like to thank the expert reviewers for their time and effort, which contributed to strengthening our manuscript.
Received March 27, 1995; first decision April 26, 1995; accepted July 18, 1995.
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