Monoamine responses to acute and chronic aerobic exercise in normotensive and hypertensive subjects

Objectives: The purpose of the present study was to compare the plasma and serum monoamine levels in sedentary, untrained normotensive and hypertensive men at rest with levels measured after an acute bout of exercise and to compare similar measurements following a 12-week aerobic training program. Place of study: The data obtained for this study was co"lIected from a clinic for the prevention of heart disease and cardiac rehabilitation (FITCOR) and analyzed in the Federal University of Sao Paulo (EPM), Laboratory of Experimental Neurology. Subjects: Two groups of untrained male subjects, i.e., normotensive (N=16) and hypertensive (N=19), were submitted to an acute bout of exercise to analyze the acute effect of exercise on the monoamine levels. To study the chronic effect of exercise (physical training program), some individuals of each group were arranged in two other groups; normotensive (N=11) and hypertensive (N=8). Measurement: Plasma catecholamines and serum serotonin levels were determined by high performance liquid chromatography coupled with electrochemical detection. Results: A significant reduction in diastolic blood pressure at rest was observed in the hypertensive group after the physical training program (p < 0.05). Only the mean plasma noradrenaline concentration increased significantly post-exercise in all groups of individuals (acute effect of exercise p < 0.01 for untrained normotensive and hypertensive; chronic effect of exercise p < 0.001 for untrained and trained normotensive, p < 0.01 for untrained and trained hypertensive). Conclusion: These data show the beneficial effect of physical exercise in reducing the blood pressure in hypertensive patients, which does not seem to be related to changes in circulating monoamines.


INTRODUCTION S
everal studies have shown that acute and chronic physical exercise, may affect catecholaminergic and serotoninergic systems (1,2,3,4).
The involvement of monoamines in hypertension has been repeatedl y reported (5).
Sympathetic nervous system overactivity is reported to be an important mechanism in the initiation of blood .pressureelevation in essential hypertension (6, 7).The  (9).Although .the mechanisms by which repeated exercise may lower blood pressure have not been clearly defined, these physiological adaptations are similar to those achieved through ~-adrenoceptor blocking.These similarities suggest that exercise lowers blood pressure through a reduction of sympathetic neural activity (9).
Like catecholamines, serotonin is also present in the peripheral system and plays its physiological role on vascular smooth muscle (10,11).It is also known that both central and peripheral serotoninergic systems are involved in cardiovascular regulation and the action of other vasoactive substances like noradrenaline and angiotensine II are amplified by serotonin.
Therefore, abnormal serotoninergic activity may participate in the pathogenesis of essential hypertension (11).
Physical training modulates the activity of these neurotransmitters at rest and during exercise, demonstrating an exponential relationship with increasing workload (12,13,14).
Since peripheral monoamines are involved in mechanisms that control blood pressure, and physical exercise affects monoaminergic systems, this work aimed at studying the involvement of monoamine levels in the beneficial effect of an aerobic training program.To achieve such goals we determined the level of circulating monoamines at rest, post-exercise and after a period of aerobic physical training in sedentary normotensive and hypertensive subjects.
Part of the data for the chronic effect of exercise was refereed in the Brazilian Journal of Medical and Biological Research (1996) in a Short Communication form.

MATERIAL AND METHODS
Two groups of untrained male subjects, i.e. .normotensive (UT/N, N=16) and hypertensive (UT/H, N=19), were submitted to an acute bout of exercise to analyze the acute effect of exercise on the monoamine levels.Some individuals of each group were arranged in two other groups (respectively TIN, N=ll and T/H, N=8) to study the chronic effects of exercise (physical training program).Since some individuals did not follow the protocol determined for the study, these were not included in studying the chronic effect of exercise.All individuals were recruited from a clinic for the prevention of heart disease and cardiac rehabilitation (FITCOR) and were informed about the study design and objective and freely decided to participate in this study.None was involved in a regular aerobic exercise program before the study or was taking medications during the physical training program.According to the World Health Organization (WHO) criteria (I5), all subjects classified as hypertensive would have a diastolic blood pressure = 95 mmHg recorded after 10 minutes in the sitting position on at least three different occasions.All measurements were made with a mercury sphygmomanometer and the diastolic blood pressure was recorded at the fifth phase of { Korotkoff's sounds.Anthropometric data (16) were obtained in the two groups (N and H) before and after the period of the physical training program.
All subjects were submitted to an ergometric test before and after the physical training program.Each subject performed a maximal treadmill test (Inbramed Mod.KT-2000) using the Ellestad protocol (17).Oxygen uptake was measured continuously during the test through the open-circuit method until exhaustion (Oxygen sensor N-22m, Oxygen analyzer S-3A11, Carbon Dioxide sensor P-61B, Carbon Dioxide analyzer CD-3A (Ametek), DTM-325-MAOP-I0 psi, American Meter).Heart rate, electrocardiogram (Hewlett -Packard System 4700 A Cardiograph) and blood pressure were measured during supine rest, during each minute of the treadmill test, and at the first, second, fourth and sixth minutes of recovery.Blood pressure recorded at rest and at the intensity of 60% of maximal oxygen uptake (V0 2 max) was considered for statistical analysis.

Sampling Procedure
The subjects were instructed not to change any dietary or sleeping habits, except for a 12 hour fast before blood sampling.Blood samples (10 ml for catecholamines and 5 ml for serotonin assay) were drawn by venipuncture from each subject in the sitting position into heparinized tubes (catecholamines) and into dry tubes (serotonin) after 20 minutes of rest pre-exercise and immediately postexercise in the sitting position, between 7:00 and 9:00 a.m., before and after the physical training program.The .dry tubes were then placed on ice for 3 hours for clot retraction and the plasma and serum was obtained by refrigerated centrifugation at 3000 g for 15 min.Plasma and serum were then stored in liquid nitrogen until assay time, for no more than two months.

Physical training program
Subjects participated in a physical training program for a period of three months (36 sessions, 3 days per week) at an intensity of 60% of maximal oxygen uptake (V0 2 max).Exercise bouts consisted of 40 minutes of aerobic exercise (20 minutes on a cycle ergometer and 20 minutes of walking and/or jogging) and 30 minutes of neuromuscular endurance exercise, flexibility and coordination.Heart rate was measured while the subject was on the cycle ergometer, walking andlor jogging at the beginning, during and at the end of all sessions of exercise in order to control the intensity of effort (60% V0 2 max) as recommended by the American College of Sports Medicine (18).The work load was adjusted during the

RESULTS
Anthropometric data are presented in table 1.There were no statistically significant differences in mean age, weight or height before and after the physical training program either in H or N groups.The sum of 7 skinfold thickness was compared between the H"and N groups and differed significantly only with the acute effect of exercise.
However, there were no significant differences in the body mass index of the same group, or between the Nand H groups before and after the physical training program.
Blood pressure -UTIN and UTIH showed significant differences in diastolic blood pressure (DBP) at rest and during .physicaleffort (figure 1).When the two groups (TIN and TIH) were compared for the chronic effect of exercise, they showed significant differences at rest before the physical training program in DBP.After the physical training program, there were no significant differences in DBP and sistolic blood pressure (SBP) between TIN and TIH.DBP was significantly reduced at rest in the TIH group (figure 2).
Monoamines -Plasma noradrenaline (NA) concentration was significantly higher post-exercise in all four groups (tables 2 and 3).Plasma adrenaline (A) and serum ser'otonin (5-HT) concentrations were not significantly changed at rest and post-exercise in any of the four groups (tables 2 and 3).Monoamine concentrations in trained groups (TIN and T/H) obtained either at rest or after exercise were not significantly different from their respective untrained groups (UT/N and UT/H).In the present study, plasma noradrenaline at rest and for the same relative work lo~d was not affected by the physical training program in the hypertensive group, although there was a tendency for higher levels after  .In agreement with our results, some investigations have demonstrated that the sympathetic nervous system activity is not increased in essential hypertension (31).By reviewing 64 studies, Goldstein (6) observed that 80% of the studies reported higher plasma noradrenaline levels in hypertensive than in normotensive subjects, but statistically significant differences were found in only about 40% of them.Considering plasma adrenaline levels, the majority of studies have shown higher adrenaline levels in hypertensive patients as compared with normotensi ve subjects, and also only about 40% of studies have reported statistically significant differences.In contrast, the correlation between physical exercise and serotonin has not been conclusively established.The serotonin response to exercise has been investigated minimally.Co'nsidering our results, probably the aerobic exercise (60% VOzmax) does not provoke significant alterations in peripheral serotonin levels.A reduction in its level would probably be necessary to suppress the vasoconstrictor effects of serotonin, and therefore, lower the blood pressure.
The results of this study suggest that aerobic exercise programs have an important effect in the reduction of blood pressure.However, this influence cannot be directly related to changes in plasma monoamines. in the rat.

Figure
Figure 2 -Blood pressure values in normotensive and hypertensive subjects at rest and during effort, before and after physical training program.Data are expressed as mean :t SO. * Statistically significant difference of DBP at rest from normotensive group before physical training program (ANOVA test) for p < 0.001 ; .**Statistically significant difference of DBP at rest after physical training program in hypertensive group (ANOVA test) for p < 0.05.DBP -Diastolic blood pressure.SBP -Systolic blood pressure.
using the heart rate to maintain appropriate exercise intensity.The blood sampling was done at the same intensity of physical effort (assessed through heart rate) before and after the physical training program.
2 -Blood pressure values in normotensive and hypertensive subjects at rest and during effort, before and after physical training program.Data are expressed as mean :t SO. * Mason lW, Hogan RP et al.Multiple hormonal 24.Wolfson S, .Acosta AE, Rose LI, Parisi AF, Engelman I. responses to graded exercise in relation to physical training.Serum serotonin levels of normal and autistic children.Brazilian 1 Med BioI Res 1993;26:309-317.intensities as related to the individual anaerobic threshold.