Hypertension is a main risk factor for coronary heart disease, heart infarction and cerebral stroke. Blood pressure reduction diminishes incidence of death from cardiovascular diseases (1). There is general agreement that essential hypertension is accompanied by an increased sympathetic cardiovascular activity (2-6), reduced parasympathetic modulations of the heart rate, and decreased heart rate variability(7-9).

Recent studies have shown that regular aerobic exercise lowers blood pressure in patients with essential hypertension (10-15,17-22) and attenuates the effects of cardiovascular risk factors (15,16). The mechanisms responsible for blood pressure reduction induced by exercise training in hypertensive subjects are still poorly understood (13,17,18). Reduced cardiac output (19,20) versus reduced total vascular resistance (18) were reported. Important contribution is apparently due to reduction in cardiovascular sympathetic activity observed in hyper- tensives after physical training (14,21,22).

Noninvasive classical methods of quantification of the cardiovascular variability, the variance and spectral analysis of systolic blood pressure and heart beat intervals provide an insight into autonomic control of the circulation in hypertensive subjects (23-27). The LF component of systolic blood pressure power spectrum (LFSBP) is considered as a marker of oscillations of the sympathetic activity addressed to resistant arteries (9,23-27). Magnitude of LFSSBP appears related to likelihood of secondary disadvantageous cardiovascular complications in essential hypertension i.e. cardiovascular remodelling and cardiac hypertrophy (27).

Iellamo (28) found in healthy people submitted to submaximal exercise training an augmented vagal cardiac modulation and a tendency to decrease sympathetic vasomotor control, suggested from decrease in the LF component of systolic blood pressure spectral power. Reduction of arterial blood pressure accompanied by lower LF component of systolic blood pressure was observed after isometric (handgrip) training in older hypertensive subjects (29). There are no reports on the effect of physical dynamic training on blood pressure oscillations power spectra in young hypertensive subjects. The pourpose of our study was to evaluate the mechanism of the hypotensive effect of physical training in mildly hypertensive young men by analysing cardiovascular variability. We compared the systolic and diastolic blood pressure (SBP and DBP respectively), pulse interval (PI), total peripheral vascular resistance (TPR), arm regional vascular resistance (AVR) and some indices of SBP and PI variability: the variance of SBP and PI and LF component of the SBP power spectrum before and after the 3-month period of dynamic physical moderate training.

Controlled physical training was performed by young mild hypertensive subjects and age matched healthy subjects.


SUBJECTS AND METHODS
Subjects

The study was approved by Ethic's Committee On Human Research of the Medical University of Warsaw. Each subject gave consent to participate in the study. Measurements were performed on 30 untreated mildly hypertensive (HTS) and 18 healthy normotensive male subjects (NTS). The normotensive subjects were mostly medical students. All participants were strongly motivated and express a desire to increase their physical fitness. Hypertensive patients were interested in decreasing the blood pressure by physical training rather than by pharmacological treatment. All subjects were clinically examined and free from pulmonary, renal and heart diseases. Characteristics of both groups are shown in Table 1.

Table 1. Baseline characteristics of the study groups

Pharmacological treatment was discontinued for at least two weeks before the start of the study. Astrand's submaximal test was used to determine physical fitness by maximal oxygen consumption.

Training

All subjects were instructed on the procedure and obtained detailed explanation how to perform by themselves individual training.

During laboratory measurements on cycloergometer the subjects observed the changing workload level and the response of heart rate (HR) to work load. The training consisted in dynamic aerobic exercise at a 40-50% of each subject VO2max .The values of HR calculated for each individual for 40 - 50% VO2max were established on the cycloergometer in the laboratory and known to each subject. The subjects performed an exercise 3 times per week for about 1 hour according to favoured kind of activity (running, cycling, tennis, swimming, volley ball, brisk walking). They controlled heart rate by themselves to maintain the level of estimated heart rate at 40-50% VO2max.

Procedures

The procedures were always carried out in the same order. Body weight and height were checked and arterial blood pressure was measured by mercury sphygmomanometer. During testing electrocardiogram leads (ECG) for heart rate, chest wall electrodes for cardiac output measurements by impedance cardiography, arm electrods for measurement arm blood flow by impedance method were attached. The Finapres cuff was put on a finger for continous blood pressure measurement. Finger arterial blood pressure was recorded by Finapres (Ohmeda, model 2300) at the level of tricuspid valve, to avoid hydrostatic influences. The method has been validated for power spectral analysis of arterial pressure variability (30). Stroke volume, cardiac output (CO) and arm muscular blood flow were recorded with tetrapolar impedance reography (Warsaw Technical University), and heart rate interval from one lead ECG, telemetry (Fukuda Denshi). All data were synchronously sampled and recorded continously with sampling freqency 200 Hz and 12-bite resolution for subsequent off-line analysis. Stroke volume and CO was calculated from the first derivative of the impedance change, using the Kubicek equation (31). TPR was calculated in TPR units by dividing mean arterial blood pressure by cardiac output. Arm regional vascular resistance was calculated per 100 ml tissue/min in PRU units. Resting measurements were performed in comfortable sitting position.

Measurement and assessment of systolic blood pressure variability

The variance of SBP and pulse interval variance were calculated from about 30 sec periods. Pulse intervals were calculated in miliseconds (ms) from Finapres data by inversion of heart rate values.

The respiratory rate was assessed by impedance method. The spectral analysis was performed with the program written for the pourpose of this study on segments of 512 consequtive points. By visual inspection stationary series, free of ectopic beats and artefacts were selected for off-line analysis. Hanning's window and fast Fourier transform (FFT) computation were used. The low frequency component of the power spectrum included the power from 0.04 to 0.15 Hz, and the high frequency component the power spectrum (HFSBP) respectively from 0.15 Hz to 0.25 Hz. The power of each band was calculated as integral of power spectral density under the curve in the frequency range. LFSBP and HFSBP were computed in absolute units in mmHg2 and in normalized units expressed as a percentage of the total power.

Exercise

After completing data collection in the control preexercise period subject rested about 10 min. Subsequently1 hour exercise of increasing intensity was performed on electric bicycle ergometer Monark 829E, up to the level of about 40-50% of each subject's VO2max. All parameters were continously registered during exercise. After exercise the subjects had a break for at least 1 hour. Thereafter they were submitted to the same sets of measurements as before exercise.

Statistical methods: Data were assessed for normal distribution by the computation of standardized skeweness and standardized kurtosis. Comparisons between NTS and HTS were made by unpaired t-test or Mann-Whitney test. Within groups differences were evaluated by paired t-test or Wilcoxon signed rank test for nonnormally distributed data. Values were expressed as mean ± SE. Linear regression analysis was used to calculate correlations. Statistical significance was assumed at p < 0.05.


RESULTS
Weight decreased and maximal oxygen uptake increased in hypertensive patients and in healthy control subjects after 3-month dynamic exercise training (Table 2). At rest the hypertensives as compared to normotensives demonstrated significantly higher systolic, diastolic blood pressure and TPR, (Table 3). Pulse interval variance was significantly lower and LFSBP significantly higher in HTS, comparing to NTS (Table 4).

Table 2. Effect of exercise training on VO2max, weight and respiratory rate in NTS and HTS

Control - the values from pre-training period , 95% CI - 95% confidence interval

Table 3. Effects of exercise training on hemodynamic pattern in normotensive(NTS) and hypertensive (HTS) subjects.

p - significance level in respect to changes within the group, * - p < 0.05 in respect to differences between groups. 95% CI - 95% confidence interval. Abbreviations - see text

The hypertensive subjects showed significant decrease in SBP and DBP after training period. In NTS decrease in SBP and DBP was insignificant. No significant change in cardiac output was observed in either group. TPR decreased significantly in both groups. AVR decreased slightly yet not significantly. Resting pulse interval and PI variance increased significantly after training in both groups (Table 4).

Table 4. Effects of exercise training on systolic blood pressure oscillations and PI variance in normotensive (NTS) and hypertensive subjects (HTS)

p - significance level in respect to changes within the group, * - p < 0.05, # p< 0.01 in respect to differences between groups. PIvar - PI variance, other descriptions - see text and Table 2

SBP variance decreased significantly only in HTS subjects (Table 4). In control period LFSBP was higher in HTS compared to NTS at rest (Table 4, Fig.1) After physical training LFSBP decreased significantly in hypertensive patients to the value not different from that in normotensive subjects (Table 4, Fig 1).

Fig.1. The effect of physical training on low-frequency component of systolic blood pressure power spectrum (LFSBP) in normotensives (NTS) and hypertensive subjects (HTS). NTSc, HTSc- the pre-training values of LFSBP for NTS and HTS respectively, NTSt, HTSt - the post-training values of LFSBP. # - p < 0.01 NTSc vs HTSc, * - p < 0.01 HTSc vs HTSt.

In HTS a correlation between LFSBP and SBP was positive: r =0.38, p < 0.001, whereas in NTS a negative: r = - 0.5 p < 0.001 (Fig.2).

Fig.2. Relationship between the LFSBP and SBP in hypertensive and normotensive subjects.

DISCUSSION
Increased LFSBP and reduced PI variance in hypertensive subjects in pre-training period are consistent with the hypothesis that dysregulation of the autonomic nervous system plays a role in the pathogenesis of hypertension (3,9). Magnitude of LFSBP appears symptomatic of increased probability of cardiovascular complications in hypertension (28). The positive correlation between LFSBP and SBP in hypertensive subjects may indicate the impairment in blood pressure autonomic control in hypertensives (Fig.2). The negative correlation between LFSBP and SBP in normotensive subjects suggests a normal negative feedback between blood pressure and sympathetic modulation of SBP exerted by baroreceptor reflex (Fig.2).

The present study supports the view that exercise trainig improves the impaired pattern of cardiovascular autonomic regulation in hypertensive subjects (11,12). Decrease in the blood pressure, the systolic blood pressure variability and in total peripheral vascular resistance, as well as increase in pulse interval duration and pulse interval variability found in the present study represent a beneficial effects of regular physical exercise on blood pressure regulation in hypertension.(11-14). The main difference in the response to 3-month training between normotensives and hypertensives found in the present study is a significantly greater decrease in blood pressure and in LFSBP in HTS as compared to NTS (Tables 3 and 4, Fig.1).

Our study showed for the first time that the decrease in arterial blood pressure and in TPR in hypertensive subjects submitted to dynamic physical exercise (Table 3) is associated with a significant decrease in LF component of SBP power spectrum (Table. 4, Fig.1).

LFSBP correlates with the overall sympathetic activity addressed to vascular system (24,26). The LFSBP corresponds to Mayer waves or SBP fluctuations with 10-sec periodicity and is related to changing sympathetic tone (23,24). LFSBP is augmented during manuevers that increase sympathetic activity, i.e. upright posture (24,25), and is diminished after alpha-adrenergic receptors blockade or ganglionic blocker trimetaphan (32). Pagani et al. (24) reported that oscillations in muscle sympathetic nerve activity recorded by microneurography were mirrored by oscillations of SBP. Sympathetic activation was associated with an increase of LF component of both SBP and muscle sympathetic nerve activity.

Augmented value of LFSBP in resting hypertensive subjects, (Table 4) was reported also in other studies (25,27). They are consistent with increase in tonic sympathetic activity found in large mild hypertensive population by use of direct microneurographic method applied to single sympathetic nerve units (2,4).

Decrease in LFSBP in HTS after training is of special interest, because it provides noninvasive insight into the mechanism of the reduction in blood pressure and TPR produced by regular physical activity in hypertensive subjects. We sugest that training-induced decrease in LFSBP in HTS depends on reduction of sympathetic nerve activity addressed to resistance arteries. This effect apparently contributes to decrease in blood pressure and in TPR in HTS. Our suggestion is in line with other observations made with the use of invasive methods (14). Decrease in LFSBP in hypertensive patients after physical training is consistent also with reported decrease in norepinephrine plasma level after physical training in HTS (14,19,21,22). Reduction in sympathetic drive that follows training appears more pronounced in patients with essential hypertension than in normotensive individuals (18). Reports on the effects of physical training on resting sympathetic vasoconstrictor nerve output to peripheral vascular bed in healthy people are not consistent (33). In healthy humans training studies report no change (34), increase (35) or decrease (36) in resting muscle sympathetic nerve activity. Mechanisms of reduced sympathetic activity produced by physical training in hypertensive subjects are still unknown (6). Attenuation of cardiovascular response to brief inactivation by hyperoxia of arterial chemoreceptors observed during postexercise hypotension suggests that chemoreceptor sympathoexcitatory reflex is reduced following physical exercise (37). It is to be checked if regular physical training induces sustained attenuation of the resting chemoreceptor pressor reflex in hypertensive subjects. Augmented chemoreceptor reflex drive appears to contribute to mechanisms of arterial hypertension (37-42). Also a facilitation of baroreceptor reflex can be taken under consideration, as an increased baroreflex sensitivity was reported after physical exercise in hypertensive subjects (11,12,37).

In hypertensives as compared to healthy men cardiovagal tone is decreased as suggested by diminished pulse interval variance, a finding consistent with other reports (7-8). Exercise training tended to reverse and normalize the hypertension-related deficits in parasympathetic tone, as PI variance significantly increased (Table 4).

Although in hypertensive subjects pulse interval variance was lower than in normotensives the pulse interval duration did not differ significantly.

Physical training results in increase in pulse interval duration and pulse interval variance - both in NTS and HTS (Table 4). No significant difference in the respective responses to physical training between two groups were observed.

We choose a moderate training level, as in recent study (28) only such training induced augmented parasympathetic cardiovascular modulation, in parallel with it a tendency to decrease power of LF component of SBP in healthy people. In contrast, high intensity training (above 75% of VO2max) elicited an increase in LFSBP and shifted the neural autonomic cardiovascular profile from vagal to sympathetic predominance (28), an effect potentially dangerous to hypertensive patients by increasing probability of the adverse circulatory consequences (3). Augmentation in parasympathetic activity with concomitant decreasing sympathetic activity is desirable in hypertensive patients and coronary artery diseased patients (5). Moreover, longitudinal epidemiological studies have shown, that low to moderate physical exercise is most effective in reducing increased blood pressure in hypertensive patients than training at a vigorous intensity (10, 13,15).

It has been documented in longitudinal studies that lowering blood pressure, even small, reduces incidence of and mortality from cardiovascular diseases (1,10, 15). Decreased pulse interval and heart rate interval variability correlates strongly with future cardiovascular events (5, 8). An increase in systolic blood pressure variability is known predictor of cardiovascular risk in patients with blood pressure elevations (44,45). Noninvasive cardiovascular indices in hypertension are of prognostic value for the cardiovascular events and progression to end organ damage (3, 5,9,27,44,45). Recently, it has been shown significant relation between short term and long term blood pressure 24-hour variability indexes (45).

Decrease in blood pressure, total peripheral resistance and increase in pulse interval and PI variance in HTS subjects observed in our study after physical training are not dissimilar to other reports (11,12,14). A novel finding of possible clinical value is a pronounced reduction of LFSBP, a noninvasive marker of sympathetic activity after physical training applied in mild hypertensive patients.

In summary we conclude that antihypertensive effects of moderate dynamic exercise training in mild hypertensive subjects are associated with readjustment of the autonomic cardiovascular control system which possibly contributes to beneficial effects of regular physical exercise in hypertension.

Acknowledgements: This study was supported by KBN Grant No 4P0 5D 60 18


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