Intermittent Hypoxia-hyperoxia Conditioning as a New Therapeutic Intervention to Reduce Hypertension

The prevalence and absolute burden of hypertension is rising worldwide and represents one of the leading modifiable risk factors for cardiovascular diseases being indirectly involved in the development of, for instance, stroke, kidney diseases, and dementia.

There is rather solid evidence supporting the assumption that intermittent and continuous hypoxia at rest or in combination with exercise is generally effective to reduce blood pressure and positively influence vascular health.

A well-designed and controlled hypoxic stimulus may induce benefits for health and is known as hypoxia conditioning (HC). Indeed, brief and repeated exposures to hypoxia trigger cellular and systemic physiological adaptations that make the organism more resilient to subsequent severe hypoxic stress, and possibly also to other stressors.

The mechanisms associated with an antihypertensive effect of moderate hypoxia may include vascular adaptions (e.g. increased vascularisation and endothelium-dependent vasodilatation) as well as adaptations in the autonomic nervous system (e.g. reduced sympathetic activity).

Hypoxia exposure leads to a multiphasic blood flow and pressure response over time. The first and immediate phase following hypoxic stimulus is characterized by a systemic vasodilation that aims to counteract the decrease in arterial oxygen (O2) content and subsequent peripheral O2 delivery. If hypoxia exposure lasts for more than few minutes, pressor mechanisms, such as sympathetic activation, a rise in arterial stiffness, an increase in endothelin-1 levels, a baroreflex dysfunction and an elevation in blood viscosity, exceed vasodilatory responses resulting in a rise of blood pressure. However, the mechanisms at the onset of the early blood pressure response are beneficial for vascular health and an improvement in vascular function following intermittent hypoxia exposure has been reported during both intermittent resting exposure (FiO2: 10-14%, 3-5 minutes of normobaric hypoxia per cycle, 3-25 cycles/day during 10 to 30 days [7]) or intermittent exposure combined with exercise (2 hrs of hypobaric hypoxic exposure (FiO2: 16.5%) with 30 minutes of moderate intensity exercise, 4 days/week during 8 weeks).