The Effect of Physical Training in the Aerobic-Anaerobic Transition Zone on Oxidative Metabolism in Patients with Arterial Hypertension

The dissertation is devoted to the investigation of the effect of physical training performed in the aerobic-anaerobic transition zone on oxidative metabolism in patients with arterial hypertension. The work substantiates the advisability of applying individualized dynamic loads of moderate intensity close to the anaerobic threshold for the correction of disorders of oxidative homeostasis, systemic hemodynamics, and endothelial function in patients with Grade I–II arterial hypertension. The mechanism of adaptive reorganization of intracellular antioxidant systems under the influence of physical loading causing transient oxidative stress is investigated.

Relevance of the Topic. Arterial hypertension (AH) is a significant cause of disability and mortality, which determines the relevance of its primary and secondary prevention (Gogin E.E., 1997; DAG-1, 2000).

Pathophysiologists regard AH as a stable maladaptation encompassing a complex of interrelated hemodynamic, metabolic, and neurohumoral disorders caused by a reduced adaptive capacity of the organism (Morman D., Heller JI., 2000; Lilli JI., 2003). One of the leading maladaptive disorders in AH, underlying endothelial dysfunction, is the imbalance between vasoconstrictors and vasodilators, and in particular, the reduced bioavailability of nitric oxide due to its neutralization by reactive oxygen species (Volgarev M.N. et al., 1993; Luscher T.F., Boulanger C.M., 1992; Comi D. et al., 1997). In this regard, special interest is represented by data on the reduced adaptive capabilities of major intracellular antioxidant enzymes in patients with AH, which leads to sustained pathological oxidative stress (accumulation of reactive oxygen species) and, consequently, vasoconstriction and peroxidative damage to the vascular wall (Elchaninova S.A. et al., 2002; Sidorenkova N. et al., 1998). It is known that even effective pharmacotherapy does not lead to complete and sustained restoration of impaired mechanisms of regulation of tone of resistance vessels in patients with AH (Bubnova M.G. et al., 2003; Kingwell V.A. 2000; Kataoka II. et al., 2001) and, in particular, does not eliminate the adaptive insufficiency of antioxidant enzymes (Elchaninova S.A. et al., 2000; Sidorenkova N. et al., 1999).

On the other hand, it has been proven that reactive oxygen species and products of lipid peroxidation can act as physiological regulators (Bokoch G.M., 1994; Imbert V. et al., 1996; Kamata II. et al., 1996; Sundaresan M. et al., 1995, 1996; Finkel T., 1998). In vitro experiments have shown that they are substrate inducers of genes of intracellular antioxidant enzymes (Inoue N. et al., 1996; Li Y.S. et al., 1996; Topper J.N. et al., 1996; Jo I. et al., 1997). This allows assuming the possibility of developing an adaptive potential of these enzymes in patients with AH through physical training accompanied by the development of hypoxia, which, as is known, enhances the production of reactive oxygen species and causes transient oxidative stress (Kritsman M.G., Konikova A.S., 1968; Ohishi S. et al., 1997; Ortenblad N. et al., 1997; Azenabor A.A. et al., 1999; Bejma J., Ji L.L., 1999).

It should be noted that physical training has long been a generally recognized effective method of treatment of AH (Yeater R.A., Ullrich I.H., 1992; DAG-1, 2000; Statement on exercise, 1993). Several different systems of physical training for patients with AH have been proposed (Efremushkin G.G. et al., 1991; Almazov V.A., Shlyakhto E.V., 2001; Weber V.R., Britton A.M., 2002; Zadionchenko B.C. et al., 2002; Lund-Johansen P, 1987; Ehsani A.A., 2001). Analysis of data on the efficacy and mechanisms of their influence showed that for the treatment of AH, the optimal application is dynamic loads of moderate intensity close to the anaerobic threshold (AT) — the minimum load intensity at increasing work intensity at which anaerobic processes begin to develop, detected by laboratory methods (the onset of the aerobic-anaerobic transition zone of energy supply of muscular activity). Individualized dosing of such intensity is feasible not only in healthy individuals but also in patients with cardiovascular pathology, since the AT constitutes no more than 50–70% of the value of maximal oxygen consumption and can therefore be determined in a functional exercise test (Aulik I.V., 1979; Seluyanov V.I. et al., 1991; Bolezni., 1992; Kudryashov V.E. et al., 2000; Wasserman K. et al., 1973; Rusko N. et al., 1980).

Comparing the above data, we concluded that in patients with AH, correction of pathogenetic disorders of oxidative homeostasis and blood pressure levels is possible through individualized physical training involving dynamic loads in the aerobic-anaerobic transition zone up to the onset of hypoxia.

Objective of the Study. To investigate the effect of physical training in the aerobic-anaerobic transition zone on oxidative metabolism in patients with arterial hypertension.

Tasks of the Study:

1. To study the change in work capacity and systemic hemodynamics parameters in healthy individuals and patients with AH under the influence of physical training in the aerobic-anaerobic transition zone.

2. To investigate the change in total prooxidant activity, concentration of thiobarbituric acid reactive products and endothelial microparticles in blood plasma, and activity of major antioxidant enzymes in erythrocytes under the influence of physical training in the aerobic-anaerobic transition zone in healthy individuals and patients with AH.

3. To evaluate the concurrence of changes in systemic hemodynamics, oxidative metabolism, and the concentration of endothelial microparticles in blood plasma in patients with AH during physical training in the aerobic-anaerobic transition zone.

Scientific Novelty. For the first time, the possibility of adaptive enhancement of the activity of major intracellular antioxidant enzymes, reduction of the severity of oxidative stress, and damage to the endothelium in patients with AH through physical training involving dynamic loads in the aerobic-anaerobic transition zone has been demonstrated.

For the first time, it has been established that physical training of patients with AH of Grade I–II in the aerobic-anaerobic transition zone exerts a hypotensive effect, reduces blood pressure variability, and contributes to the development of aerobic work capacity.

Practical Significance of the Work. The efficacy of treatment of Grade I–II AH through physical training in the aerobic-anaerobic transition zone according to the methodology of Ladanov P.I. et al. (2000) has been substantiated. The clinical-diagnostic significance of determination of total prooxidant activity, concentration of thiobarbituric acid reactive products and endothelial microparticles in blood plasma, as well as activity of major antioxidant enzymes in erythrocytes in the treatment of AH has been confirmed.

Implementation of the Results of the Work. Scientific and practical developments presented in the dissertation are used at the Department of Biochemistry and Clinical Laboratory Diagnostics of Altai State Medical University in the educational process, as well as in practical healthcare based on the cardiology department of City Hospital No. 1 of the city of Barnaul.

Main Propositions for Defense:

1. Physical training involving dynamic loads in the aerobic-anaerobic transition zone is effective for the development of aerobic work capacity and correction of the level and variability of blood pressure in patients with AH of Grade I–II.

2. Mechanisms of the effect of physical training in the aerobic-anaerobic transition zone in patients with AH of Grade I–II include correction of disorders of oxidative metabolism — enhancement of the activity of major intracellular antioxidant enzymes, reduction of the severity of oxidative stress, and damage to the endothelium.

3. Physical training of healthy individuals involving dynamic loads in the aerobic-anaerobic transition zone is capable of developing work capacity and enhancing the activity of major intracellular antioxidant enzymes.