Introduction
Interest in intermittent hypoxia’s effects has remained high for decades. In the 1970s it became known that hypoxic stimuli activate vital systems and intermittent exposure produces comprehensive adaptive restructuring [1–3]. Intermittent hypoxic training (IHT) is therefore widely used to increase nonspecific resistance [4–6]. Its biochemical effects in humans remain insufficiently studied. Hypoxia can increase reactive oxygen species and lipid-peroxidation products, inducing oxidative stress [7], which can enhance expression of major antioxidant enzyme genes: superoxide dismutase (SOD), catalase and glutathione peroxidase (GP) [8]. We hypothesised that intermittent oxidative stress increases antioxidant activity as one mechanism of IHT.
Oxidative stress participates in over 100 diseases and pathological states, including essential hypertension [9]. In hypertension, reactive oxygen species disrupt arterial structure and function: they inactivate nitric oxide and reduce vasodilation, irreversibly damage vessel walls through peroxidation and stimulate remodelling. Oxidative stress is attributed both to greater production by vascular-cell enzymes and to an inert antioxidant enzyme system [10]. It was therefore important to study reactive oxygen metabolism under IHT in healthy people and hypertensive patients.
Methods
Participants were 20 practically healthy people, six men and fourteen women aged 40 ± 2, and 20 stage I–II hypertensive patients, seven men and thirteen women aged 43 ± 3, according to WHO 1996 classification. With standard antihypertensive therapy, blood pressure had remained at or below 145/85 mmHg for 2–3 months. This allowed reliable assessment of IHT, difficult during decompensation requiring rapid medication changes.
The Bio-Nova-204 installation delivered 14 daily one-hour sessions. Mask breathing of a 10–12 vol.% oxygen mixture for 1–5 minutes alternated with atmospheric air for 1–5 minutes.
Before IHT, one day after the final session and again after 3–4 days, plasma oxidative stress was assessed by thiobarbiturate-reactive products and total prooxidant activity, the latter through product accumulation in a Tween-80 system [11]. Erythrocyte haemolysate SOD was measured by inhibition of nitroblue tetrazolium reduction by superoxide generated through phenazine methosulphate and nicotinamide dinucleotide interaction [12]; catalase by inhibition of molybdate oxidation by hydrogen peroxide [12]; and GP by loss of reduced glutathione during oxidation by tert-butyl hydroperoxide [13].
Results and discussion
Before IHT, hypertensive patients had substantially greater total prooxidant activity (1.8-fold) and thiobarbiturate-reactive products (1.7-fold) than healthy participants. Marked oxidative stress coexisted with reduced antioxidant enzyme activity, confirming earlier evidence that antioxidant capacity inadequately matches reactive oxygen production in hypertension [10].
Tables 1 and 2 show strong IHT effects on all reactive oxygen metabolism indicators in both groups. Their post-course dynamics were similar: oxidative-stress markers increased on day one, then decreased. SOD, catalase and GP initially fell moderately and transiently, then rose. This suggests increased reactive oxygen production with associated functional activation of antioxidant enzymes. Similar hypoxic preconditioning effects have been reported experimentally [14, 15]. Given substrate-induced enzyme biosynthesis, accumulated reactive oxygen species may have caused increased enzyme activity.
Thus changes followed the same direction in both groups. Hypertensive patients nevertheless had higher prooxidant activity and thiobarbiturate-reactive products and lower enzyme activity on day one and days 3–4 than healthy participants. This probably reflects hypoxia-induced reactive oxygen production superimposed on pre-existing stress. These metabolic changes did not alter blood pressure or worsen well-being. The enzyme increases on days 3–4 are important for hypertensive pathogenesis: reactive oxygen metabolism then almost matched healthy participants’ pre-IHT state.
Conclusion
IHT can develop antioxidant enzyme function from different baseline capacities. This probably contributes importantly to adaptive metabolic changes. Its enzyme effects may involve gene-expression induction by enzyme substrates, reactive oxygen species, and lipid-peroxidation products. The findings support moderate intermittent oxidative-stress training for preventing and treating maladaptive disorders driven by oxidative stress.
Publication information
S.A. Elchaninova, I.V. Smagina, N.A. Korenyak, B.Ya. Varshavsky. Effects of intermittent hypoxic training on lipid peroxidation and antioxidant enzyme activity. Human Physiology. 2003;29(3):72–75. Altai State Medical University, Barnaul. Received 28 May 2002.
References
1. Меерсон Ф.З. Общий механизм адаптации и профилактики. М.: Медицина, 1973. 180 с.
2. Стрелков Р.Б., Караш Ю.А., Чижов А.Я. и др. Метод повышения неспецифической резистентности организма с помощью нормобарической гипокси-ческой стимуляции. М., 1985. 10с.
3. Агаджанян Н.А. Организм и газовая среда обитания. М.: Медицина, 1972. 246 с.
4. [В оригинале № 1] Леутин В.П., Платонов Я.Г., Диверт Г.М. и др. Инверсия полушарного доминирования как психофизиологический механизм интервальной гипоксической тренировки // Физиология человека. 1999. Т. 25. № 3. С. 65.
5. [В оригинале № 2] Колчинская А.З. Интервальная гипоксическая тренировка (эффективность, механизмы действия). Киев: КГИФК, 1992. С. 108.
6. [В оригинале № 3] Караш Ю.М., Стрелков Р.Б., Чижов А.Я. Нормобарическая гипоксия в лечении, профилактике и реабилитации. М.: Медицина, 1988. 352 с.
7. Pavliuk N.V., Krysko О.М., Klymyshyn N.I. et al. State of antioxidant and oxygen transport system of the blood in the process of adaptation of the body to hypoxic hypoxia // Ukr. Biokhim. Zh. 1998. V. 70. № 4. P. 58.
8. Franco A.A., Odom R.S., Rando Т.А. Regulation of antioxidant enzyme gene expression in response to oxidative stress and during differentiation of mouse skeletal muscle // Free Radic. Biol. Med. 1999. V. 27. № 9–10. P. 1122.
9. Зенков Н.К., Ланкин В.З., Меньшикова Е.Б. Окислительный стресс: биохимический и патофизиологический аспекты. М.: МАИК “Наука/Интерпериодика”, 2001. С. 198.
10. Sidorenkova N., Warshavsky В., Eltchaninova S. et al. Oxidant and antioxidant status in patient with essential hypertension // J. Hypertension. 1998. V. 16. Suppl. 2. P. 211.
11. Галактионова Л.П., Ельчанинова С.А., Молчанов А.В., Варшавский Б.Я. Состояние перекисного окисления у больных с язвенной болезнью желудка и двенадцатиперстной кишки // Клин. лаб. диагностика. 1998. № 6. С. 10.
12. Чевари С., Андял Т.. Штренгер Я. Определение антиоксидантных параметров крови и их диагностическое значение в пожилом возрасте // Лаб. дело. 1991. № 10. С. 11.
13. Моин В.М. Простой и специфический метод определения активности глутатионпероксидазы в эритроцитах // Лаб. дело. 1986. № 12. С. 724.
14. Duan С., Yan F., Song X., Lu G.W. Changes of superoxide dismutase, glutathione perioxidase and lipid peroxides in the brain of mice preconditioned by hypoxia // Biol. Signals Recept. 1999. V. 8. № 4–5. P. 256.
15. Ohman Т., Parish G., Jackson R.M. Hypoxic modulation of manganese superoxide dismutase promoter activity and gene expression in lung epithelial cells // Am. J. Respir. Cell Mol. Biol. 1999. V. 21. № 1. P. 119.
Full translation of the authors’ main text: Elchaninova et al. Human Physiology. 2003;29(3):72–75.
Elchaninova et al. Human Physiology. 2003;29(3):72–75 — PDF
Related resources
Related resources explain intermittent training principles, equipment and applications.