Physiological and Clinical Implications of Adrenergic Pathways at High Altitude

Abstract

The adrenergic system is part of a full array of mechanisms allowing the human body to adapt to the hypoxic environment. Triggered by the stimulation of peripheral chemoreceptors, the adrenergic centers in the medulla are activated in acute hypoxia and augment the adrenergic drive to the organs, especially to the heart, leading to tachycardia. With prolonged exposure to altitude hypoxia, the adrenergic drive persists, as witnessed by elevated blood concentrations of catecholamines and nerve activity in adrenergic fibers. In response to this persistent stimulation, the pathways leading to the activation of adenylate cyclase are modified. A downregulation of β-adrenergic and adenosinergic receptors is observed, while muscarinic receptors are upregulated. The expression and activity of Gi and Gs proteins are modified, leading to a decreased response of adenylate cyclase activity to adrenergic stimulation. The clinical consequences of these cellular and molecular changes are of importance, especially for exercise performance and protection of heart function. The decrease in maximal exercise heart rate in prolonged hypoxia is fully accounted for the observed changes in adrenergic and muscarinic pathways. The decreased heart rate response to isoproterenol infusion is another marker of the desensitization of adrenergic pathways. These changes can be considered as mechanisms protecting the heart from a too high oxygen consumption in conditions where the oxygen availability is severely reduced. Similarly, intermittent exposure to hypoxia has been shown to protect the heart from an ischemic insult with similar mechanisms involving G proteins and downregulation of β receptors. Other pathways with G proteins are concerned in adaptation to hypoxia, such as lactate release by the muscles and renal handling of calcium. Altogether, the activation of the adrenergic system is useful for the acute physiological response to hypoxia. With prolonged exposure to hypoxia, the autonomous nervous system adapts to protect vital organs, especially the heart, against a too high energetic state, via a purely local autoregulation mechanism necessary for the preservation of overall homeostasis.

The Effect of Sex on Heart Rate Variability at High Altitude

“…This was because of the large sample size for this type of remote field study and the need to undertake at HRV in the early morning pre-breakfast and caffeine. We measured five minute HRV which may be more vulnerable to short-term sex and situational bias than that obtained from longer recordings (22). However, five minute HRV measurement is well-validated and endorsed by the current HRV Task Force Guidelines and is more potentially applicable to clinical practice than that of longer recordings (22).…”

“…An area of recent interest has been in the effects of high altitude (HA) on HRV (6)(7)(8)20). HA exposure challenges several physiological systems that are heavily reliant on continuous autonomic control and are likely to influence HRV (7,8,21,22). Acute hypoxia and HA leads to marked sympathetic activation yet paradoxically there is also evidence of increased competing parasympathetic activity which contributes to the reduction in maximal heart rate in proportion to the altitude gained (7,8,19,21).…”

Vascular homeostasis at high‐altitude: role of genetic variants and transcription factors

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Molecular pathways of oestrogen receptors and β‐adrenergic receptors in cardiac cells: Recognition of their similarities, interactions and therapeutic value

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