Background and objective
Recent studies show that intermittent normobaric hypoxia (INH) lowers blood pressure in essential hypertension [1] and normalizes cerebral blood flow, correcting cognitive dysfunction and sleep disturbance [2]. Its mechanisms, including effects on vascular tone regulation, are being intensively investigated.
Current concepts assign a key role to endothelial dysfunction and injury [3], caused in part by insufficient antioxidant enzymes [4]. This allows reactive oxygen species to accumulate, producing oxidative stress, neutralizing nitric oxide and causing peroxidative vascular injury. We previously showed that INH increases reactive oxygen species production, inducing adaptive increases in the major intracellular antioxidant enzymes in healthy people [5]. Together with hypoxic induction of angiogenic factors stimulating endothelial proliferation [6], these findings suggest that circulatory adaptation in hypertension may involve less oxidative endothelial injury and enhanced repair. The study therefore assessed endothelial injury and repair markers and oxidative homeostasis under INH in essential hypertension.
Patients and methods
Participants had grade I essential hypertension: nine men and 21 women, aged 44±2 years, with no more than one or two additional cardiovascular risk factors according to DAG 1, 2000. They received no antihypertensives for at least three weeks before enrollment or during the study. No patients withdrew early for clinical reasons. Controls were 30 normotensive volunteers, 10 men and 20 women, aged 40±4 years without documented chronic circulatory disease.
The Bio-Nova-204 system provided 20 daily sessions, each comprising six ten-minute cycles alternating a hypoxic gas mixture containing 10–12% oxygen by volume with atmospheric air.
Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were measured by enzyme immunoassay before INH and one, two, four and 14 days after the last session in all participants. In hypertensive patients, blood pressure by Korotkov’s method and bulbar conjunctival microcirculation by noninvasive microscopy were assessed before and after training. Plasma total prooxidant activity, thiobarbituric acid-reactive products and endothelial microparticles were also measured, the latter by flow cytometry with FITC-labeled CD31 antibodies. Erythrocyte superoxide dismutase, catalase and glutathione peroxidase activities were determined.
Blood pressure and microcirculation
After INH, systolic pressure decreased from 155.6±1.5 to 137.5±1.2 mmHg and diastolic from 101.5±1.0 to 87.7±0.9 mmHg, both p<0.05. Conjunctival microscopy showed microvascular changes scored as a conjunctival index. Before INH, the index was higher in hypertension than in healthy individuals, 12.2±1.1 versus 2.7±0.1 points (p<0.001). It decreased to 8.2±0.7 after INH (p<0.05), mainly through reduced perivascular edema, more uniform venular caliber and less tortuosity, an increased arteriolar-to-venular ratio, and fewer empty capillary zones and signs of blood sludging.
Antioxidant enzymes and growth factors
Before INH, superoxide dismutase activity was reduced by 18% (p<0.05), catalase twofold, and glutathione peroxidase by 14% (p<0.05). Four days afterwards all increased. Baseline plasma prooxidant activity and thiobarbituric acid-reactive products, an indirect marker of peroxidative vascular injury, were substantially elevated. Endothelial microparticles, indicating endothelial injury, were also elevated. All three decreased four days after INH.
All participants showed a 27% increase in VEGF on the first day after hypoxic therapy, followed by a decrease on day two. A second increase occurred on day four, returning to baseline by day 14.
The bFGF response differed: a modest 16% increase on day one was followed by a gradual decrease by day four. Throughout the study, VEGF concentrations were higher in hypertensive patients than healthy participants.
Conclusion
The findings suggest that INH in essential hypertension reduces reactive-oxygen-mediated endothelial peroxidative injury by developing antioxidant enzyme adaptation and stimulates endothelial cell proliferation.
References
Full main-text translation of: Ельчанинова С.А., Павловская Л.И., Кореняк Н.А., Дрягина И.В., Макаренко В.В., Симонова О.Г. Механизмы гипотензивного эффекта прерывистой нормобарической гипоксии при артериальной гипертензии. С.64–66. Санаторий «Барнаульский», Алтайский государственный медицинский университет.
Related resources
Related resources cover technology, equipment and applications.