Background:

Arterial hypertension is of central importance as a direct risk factor in the origin of numerous cardiovascular diseases. By increasing blood pressure, a number of primary and secondary risk factors also contribute indirectly to a worsening of the cardiovascular risk profile. Systematic antihypertensive therapy should thus be initiated to prevent cardiovascular events and sequelae. The current therapy guidelines from the WHO and the German Hypertension Society recommend physical activity and sport as a first line therapy; however, individual therapy plans are not specified. Furthermore, while a wealth of data are available concerning the effects of medication interventions, little attention has been devoted to the effects of physical activity and sport on the cardiovascular system in cases of pre-existing hypertension. As the foundation of systematic hypertensive therapy, an appropriate change in lifestyle is generally recommended, including a low-salt and low-fat diet, giving up smoking, and taking up physical activity. To what extent physical training alone contributes to a reduction in blood pressure can only be estimated with difficulty, because with a change in lifestyle a number of factors are changed in parallel. An animal model enables these influencing factors to be specifically controlled.

Methods:

The effect of physical activity on blood pressure and cardiac remodelling was investigated in female spontaneously hypertensive rats (SHR) at different ages. Over a period of 6 months animals were given access to an exercise wheel. mRNA and protein expression of genes linked to metabolism, hypertrophy, apoptosis and fibrosis were quantified by real time RT-PCR and Western Blot. Training data has been continuously recorded, while the blood pressure and pulse rate has been determined each week during a non-invasive blood pressure measurement using the tail cuff method. Haemodynamics, morphology and function has been assessed at intervals of three months using echocardiography.

Results:

In a first sub-project the effect of physical activity on blood pressure and cardiac remodelling was investigated in 12-month-old SHR. The voluntary mean weekly running distance was 47 km and the mean speed was 2.9 km/h. From the 20th week onwards the animals increasingly exhibited symptoms of decompensated heart failure with ascites and dyspnoea, which was reflected in a significantly increased mortality rate. The hearts showed disseminated microinfarctions, exercise-induced myocardial hypertrophy, and clear development of fibrosis. Although the running led to a significant reduction in the resting heart rate, it had no effect on blood pressure. Despite improved mitochondrial oxidation and upregulation of eNOS, running as the sole therapy accelerated cardiac decompensation by increasing pressure and volume stress.

Next the effects of 6 months’ training on an exercise wheel on the development of hypertension and on the cardiovascular system were investigated in young pre-hypertensive SHRs. The weekly running distance was 56 km and the mean speed was 2.5 km/h. Again exercise was not able to affect the development, nor the absolute level of blood pressure. In young SHR training led to an improvement of the Fractional Shortening (35.1% vs. 28.6%, p<0.05) and of the mitochondrial oxidation. However, as already shown for old SHR hearts of young animal displayed higher values of fibrotic proteins (Collagen I 3.9-fold, collagen III 284.8-fold, p<0.05). Fibrosis in turn was responsible for a worsening of the E/A Ratio during six months’ training (from 1.61 to 2.03 (p<0.05)).

Conclusion:

Both pre-hypertensive SHR and senescent animals with established hypertension cannot compensate for haemodynamic stresses caused by exercise and thus cannot benefit from the appropriate cellular adaptation mechanisms.