Short-term Strenuous Exercise Training: Effects on Blood Pressure and Hormonal Levels in Mild Hypertension P. A. Sullivan, C. Grosch, D. Lawless, D. T. O'Connor*
Mallow General Hospital, Mallow, Co. Cork, Ireland and *the Veteran's Administration Medical Centre, San Diego. California, U.S.A. Summary The effect of a six-week strenuous exercise training programme (modified Bruce protocol, treadmill, three times per week) on resting and exercising blood pressure, heart rate, plasma catecholamines, r A, renin activity and aldosterone levels was investigated in 15 patients with mild hypertension. An identical exercise test was conducted at baseline and study close (six weeks). At follow-up, seven to ten days after study close, patients completed an exercise test of equivalent intensity to that at baseline, achieving comparable heart rate levels at maximal exercise. On each occasion, blood pressure, heart rate and hormonal variables were measured at rest (supine), maximal exercise and ten minutes after stopping exercise. Resting and exercising blood pressure and heart rate were reduced by the six-week exercise regimen. There was a trend, although not statistically significant, for resting plasma noradrenaline levels to be lower at study close. The redaction in blood pressure and heart rate at maximal exercise was associated with a significant attenuation of the plasma renin response to exercise. Plasma catecholamines also appeared to be lower after exercise training, although this effect was not statistically significant. Plasma levels of chromogranin A and aldosterone measured at rest and maximal exercise were not influenced by the exercise regimen. Further controlled studies are required to corroborate the results of this preliminary study. Introduction Exercise training has been advocated as an effective nonpharmacological intervention for blood pressure control in mild hypertensionL A reduction in sympathetic tone has been mainly implicated in this response2"s,although changes in intravascular volume6 and cardiac output7 may also be involved. Additionally, the intensity and duration of the exercise programme may influence hormonal and haemodynamic effects. Mild to moderate submaximal exercise, over a period of between three and 12 months has been shown to have beneficial effects on blood pressure and haemodynamics and sympathetic toners. However, there has been limited investigation of programmes involving exercise of increased intensity over a shorter period. In an initial reports we have shown that a six-week training programme involving three strenuous exercisetraining sessions per week, each of less than 20 minutes, lowered both resting and exercising blood pressure in patients with mild hypertension. To provide some insight into the mechanism of this response, we have measured different indices of activity of the sympathetic system, noradrenaline (NA), adrenaline (A) and chromogranin A (CgA), a protein synthesized in sympathetic axons and the adrenal medulla and released in response to increased sympathetic activity9, and the renin-angiotensin-aldosterone (RAA) system,
aldosterone and renin activity, before and after completion of the study. Blood pressure and hormonal responses to the same relative exercise intensity as at baseline were also measured seven to ten days after study completion.
Patients and Methods
Patients Fifteen male patients (mean age + SEM, 42.3 + 1.0 years, range 34-54 years), with mild uncomplicated essential hyper~nsion (supine diastolic blood pressure _>85 mm Hg) participated in the study. A diastolic blood pressure of at least 85 mm Hg was defined as hypertensive as mortality has already been shown to be elevated at this level 1~ No patient was on any antihypertensive medication at the time of the study; 11 patients were new hypertensives and in the remaining four patients therapy had been withdrawn at least three months prior to an initial screening period. All patients had a sedentary lifestyle and had not participated in regular vigorous exereise for over one year. Patients were instructed to maintain their usual diet, tobacco and alcohol consumption and usual life style during the study. Patients with a personal or family history of cardiovascular or cerebrovaseular disease, with clinical evidence of secondary hypertension, or who were unable to participate in regular treadmill exercise were excluded. The study was approved by the ethics committee of Mallow General Hospital, and all patients gave informed consent before entry.
Address for correspondence to: Dr. P. A. Sullivan, Mallow General Hospital, Mallow. Co. Cork, Ireland.
Study design All patients were seen at two-weekly intervals during a six-week pre-study screening period to confirm blood 666
Vol. 161 No. 12
Short-term strenuous exercise training 667 TABLE 1 Exercise protocol (training and test days)
Stage
TABLE II Resting (supine) characteristics of evaluable patients. Data are given as mean _+ SEM.
Duration (rains)
Speed (km/hr)
1
3
2.7
Gradient (%) 4
II Ill IV V VI
3 3 3 3 3
4.0 5.4 6.7 6.7 6.7
8 12 16 20 24
Variables
pressure entry criteria, and to familiarise themselves with the exercise testing equipment and procedures. A formal self-limited exercise test, modified Bruce protocol, treadmill, as given in Table I, was conducted at baseline (end of screening period), study close (six weeks) and followup, seven to ten days after study close. During the six weeks of the study, the exercise protocol was repeated three times per week, with the duration of exercise increased by one minute at the end of each week. At the final exercise test given at follow-up (seven to ten days after the end of the six-week training period), the intensity of exercise was increased so that each patient achieved a heart rate at peak exercise equivalent to that at baseline in the untrained state. All patients abstained from food, alcohol, caffeine and tobacco for at least four hours before each exercise test or training period. Exercise testing was performed at constant temperature (18-22~ and the same time of day for each patient. Blood pressure and heart rate measurements and blood sampling were undertaken during each exercise test at baseline, study close and follow-up. Following catheterisation of the left antecubital vein, patients rested quietly (supine position) in the exercise laboratory for 15 minutes. Systolic and diastolic blood pressure (by random zero sphygmomanometer, Hawksley Instruments) and heart rate (from the electrocardiogram) were measured in triplicate at the end of this time, and mean values recorded. Blood samples were taken for the measurement of plasma NA, A, CgA, aldosterone and renin activity. Patients then stood for two minutes and blood pressure and heart rate measurements were repeated. During exercise testing, blood pressure (by standard mercury sphygmomanometer) and heart rate were measured between the second and third minute of each exercise stage, immediately before stopping exercise (maximal exercise), and five and ten minutes during recovery. Blood sampling was repeated at maximal exercise and five and ten minutes during recovery.
Sample processing and analysis Blood samples were collected in pre-chilled tubes on ice, and immediately centrifuged at 1000 rpm. Duplicate sets of plasma samples were stored at-20~ or in liquid nitrogen (for NA) until analysis. Plasma NA and A were measured by radioenzymatic assayn and plasma CgA and renin activity by radioimmunoassay, according to methods of O'Connor et al (1989) ~2and Haber et al (1969) ~3respectively. Plasma
Blood pressure (mm Hg)
Baseline
Study Close
Fellow-up
148_+4
143_+5"
137_+5"
97+2 73_+3
89_+3* 67_+3*
89+3* 67_+3*
Heart rate (beats/min) Weight (kgs) 86.5_+2.7 86.6_+2.6 Noradrenaline (pg/ml) 618+103 506+.+.+~4 Adrenaline (pg/ml) 282~_52 212_+32 Chxomogranin A 33.6-+5.0 34.2_+5.6 (ng/ml) Renin activity 1.90-20.3 1.82-+0.4 (ng/ml/hr) Atdosterone (ng/ml) 0.14-+0.01 0.13_+0.02
86.5+_2.6 449i-_50 253+37 35.0_+6.0 1.94_+0.4 0.14_+0.02
*p < 0.05 aldosterone was determined by a kit method (Diagnostic Products).
Statistics All data are given as mean + SEM. Differences between the study variables measured at baseline, study close and follow-up, were evaluated by multivariate analysis of variance with repeated measures (ANOVA). The standard error of the difference between the means was determined when the ANOVA result was significant (19
Mallow General Hospital, Mallow, Co. Cork, Ireland and *the Veteran's Administration Medical Centre, San Diego. California, U.S.A. Summary The effect of a six-week strenuous exercise training programme (modified Bruce protocol, treadmill, three times per week) on resting and exercising blood pressure, heart rate, plasma catecholamines, r A, renin activity and aldosterone levels was investigated in 15 patients with mild hypertension. An identical exercise test was conducted at baseline and study close (six weeks). At follow-up, seven to ten days after study close, patients completed an exercise test of equivalent intensity to that at baseline, achieving comparable heart rate levels at maximal exercise. On each occasion, blood pressure, heart rate and hormonal variables were measured at rest (supine), maximal exercise and ten minutes after stopping exercise. Resting and exercising blood pressure and heart rate were reduced by the six-week exercise regimen. There was a trend, although not statistically significant, for resting plasma noradrenaline levels to be lower at study close. The redaction in blood pressure and heart rate at maximal exercise was associated with a significant attenuation of the plasma renin response to exercise. Plasma catecholamines also appeared to be lower after exercise training, although this effect was not statistically significant. Plasma levels of chromogranin A and aldosterone measured at rest and maximal exercise were not influenced by the exercise regimen. Further controlled studies are required to corroborate the results of this preliminary study. Introduction Exercise training has been advocated as an effective nonpharmacological intervention for blood pressure control in mild hypertensionL A reduction in sympathetic tone has been mainly implicated in this response2"s,although changes in intravascular volume6 and cardiac output7 may also be involved. Additionally, the intensity and duration of the exercise programme may influence hormonal and haemodynamic effects. Mild to moderate submaximal exercise, over a period of between three and 12 months has been shown to have beneficial effects on blood pressure and haemodynamics and sympathetic toners. However, there has been limited investigation of programmes involving exercise of increased intensity over a shorter period. In an initial reports we have shown that a six-week training programme involving three strenuous exercisetraining sessions per week, each of less than 20 minutes, lowered both resting and exercising blood pressure in patients with mild hypertension. To provide some insight into the mechanism of this response, we have measured different indices of activity of the sympathetic system, noradrenaline (NA), adrenaline (A) and chromogranin A (CgA), a protein synthesized in sympathetic axons and the adrenal medulla and released in response to increased sympathetic activity9, and the renin-angiotensin-aldosterone (RAA) system,
aldosterone and renin activity, before and after completion of the study. Blood pressure and hormonal responses to the same relative exercise intensity as at baseline were also measured seven to ten days after study completion.
Patients and Methods
Patients Fifteen male patients (mean age + SEM, 42.3 + 1.0 years, range 34-54 years), with mild uncomplicated essential hyper~nsion (supine diastolic blood pressure _>85 mm Hg) participated in the study. A diastolic blood pressure of at least 85 mm Hg was defined as hypertensive as mortality has already been shown to be elevated at this level 1~ No patient was on any antihypertensive medication at the time of the study; 11 patients were new hypertensives and in the remaining four patients therapy had been withdrawn at least three months prior to an initial screening period. All patients had a sedentary lifestyle and had not participated in regular vigorous exereise for over one year. Patients were instructed to maintain their usual diet, tobacco and alcohol consumption and usual life style during the study. Patients with a personal or family history of cardiovascular or cerebrovaseular disease, with clinical evidence of secondary hypertension, or who were unable to participate in regular treadmill exercise were excluded. The study was approved by the ethics committee of Mallow General Hospital, and all patients gave informed consent before entry.
Address for correspondence to: Dr. P. A. Sullivan, Mallow General Hospital, Mallow. Co. Cork, Ireland.
Study design All patients were seen at two-weekly intervals during a six-week pre-study screening period to confirm blood 666
Vol. 161 No. 12
Short-term strenuous exercise training 667 TABLE 1 Exercise protocol (training and test days)
Stage
TABLE II Resting (supine) characteristics of evaluable patients. Data are given as mean _+ SEM.
Duration (rains)
Speed (km/hr)
1
3
2.7
Gradient (%) 4
II Ill IV V VI
3 3 3 3 3
4.0 5.4 6.7 6.7 6.7
8 12 16 20 24
Variables
pressure entry criteria, and to familiarise themselves with the exercise testing equipment and procedures. A formal self-limited exercise test, modified Bruce protocol, treadmill, as given in Table I, was conducted at baseline (end of screening period), study close (six weeks) and followup, seven to ten days after study close. During the six weeks of the study, the exercise protocol was repeated three times per week, with the duration of exercise increased by one minute at the end of each week. At the final exercise test given at follow-up (seven to ten days after the end of the six-week training period), the intensity of exercise was increased so that each patient achieved a heart rate at peak exercise equivalent to that at baseline in the untrained state. All patients abstained from food, alcohol, caffeine and tobacco for at least four hours before each exercise test or training period. Exercise testing was performed at constant temperature (18-22~ and the same time of day for each patient. Blood pressure and heart rate measurements and blood sampling were undertaken during each exercise test at baseline, study close and follow-up. Following catheterisation of the left antecubital vein, patients rested quietly (supine position) in the exercise laboratory for 15 minutes. Systolic and diastolic blood pressure (by random zero sphygmomanometer, Hawksley Instruments) and heart rate (from the electrocardiogram) were measured in triplicate at the end of this time, and mean values recorded. Blood samples were taken for the measurement of plasma NA, A, CgA, aldosterone and renin activity. Patients then stood for two minutes and blood pressure and heart rate measurements were repeated. During exercise testing, blood pressure (by standard mercury sphygmomanometer) and heart rate were measured between the second and third minute of each exercise stage, immediately before stopping exercise (maximal exercise), and five and ten minutes during recovery. Blood sampling was repeated at maximal exercise and five and ten minutes during recovery.
Sample processing and analysis Blood samples were collected in pre-chilled tubes on ice, and immediately centrifuged at 1000 rpm. Duplicate sets of plasma samples were stored at-20~ or in liquid nitrogen (for NA) until analysis. Plasma NA and A were measured by radioenzymatic assayn and plasma CgA and renin activity by radioimmunoassay, according to methods of O'Connor et al (1989) ~2and Haber et al (1969) ~3respectively. Plasma
Blood pressure (mm Hg)
Baseline
Study Close
Fellow-up
148_+4
143_+5"
137_+5"
97+2 73_+3
89_+3* 67_+3*
89+3* 67_+3*
Heart rate (beats/min) Weight (kgs) 86.5_+2.7 86.6_+2.6 Noradrenaline (pg/ml) 618+103 506+.+.+~4 Adrenaline (pg/ml) 282~_52 212_+32 Chxomogranin A 33.6-+5.0 34.2_+5.6 (ng/ml) Renin activity 1.90-20.3 1.82-+0.4 (ng/ml/hr) Atdosterone (ng/ml) 0.14-+0.01 0.13_+0.02
86.5+_2.6 449i-_50 253+37 35.0_+6.0 1.94_+0.4 0.14_+0.02
*p < 0.05 aldosterone was determined by a kit method (Diagnostic Products).
Statistics All data are given as mean + SEM. Differences between the study variables measured at baseline, study close and follow-up, were evaluated by multivariate analysis of variance with repeated measures (ANOVA). The standard error of the difference between the means was determined when the ANOVA result was significant (19
