Age protects from harmful effects produced by chronic intermittent hypoxia

Abstract

Obstructive sleep apnoea (OSA) affects an estimated 3–7% of the adult population, the frequency doubling at ages >60–65 years. As it evolves, OSA becomes frequently associated with cardiovascular, metabolic and neuropsychiatric pathologies defining OSA syndrome (OSAS). Exposing experimental animals to chronic intermittent hypoxia (CIH) can be used as a model of the recurrent hypoxic and O2 desaturation patterns observed in OSA patients. CIH is an important OSA event triggering associated pathologies; CIH induces carotid body (CB)-driven exaggerated sympathetic tone and overproduction of reactive oxygen species, related to the pathogenic mechanisms of associated pathologies observed in OSAS. Aiming to discover why OSAS is clinically less conspicuous in aged patients, the present study compares CIH effects in young (3–4 months) and aged (22–24 months) rats. To define potential distinctive patterns of these pathogenic mechanisms, mean arterial blood pressure as the final CIH outcome was measured. In young rats, CIH augmented CB sensory responses to hypoxia, decreased hypoxic ventilation and augmented sympathetic activity (plasma catecholamine levels and renal artery content and synthesis rate). An increased brainstem integration of CB sensory input as a trigger of sympathetic activity is suggested. CIH also caused an oxidative status decreasing aconitase/fumarase ratio and superoxide dismutase activity. In aged animals, CIH minimally affected CB responses, ventilation and sympathetic-related parameters leaving redox status unaltered. In young animals, CIH caused hypertension and in aged animals, whose baseline blood pressure was augmented, CIH did not augment it further. Plausible mechanisms of the differences and potential significance of these findings for the diagnosis and therapy of OSAS are discussed.

Contribution of adenosine and ATP to the carotid body chemosensory activity in ageing

“…; Quintero et al . ). In line with these results we found here that the basal level of CSN activity was unchanged with age, but when hypoxia was applied the response in the old animals was markedly decreased for all hypoxic levels tested (Fig.…”

“…However, at least in chronic intermittent hypoxia age exerts a neuroprotective effect against its harmful effects, since in aged rats chronic intermittent hypoxia does not alter carotid body responses, catecholamine‐related parameters or redox status, and does not cause hypertension (Quintero et al . ). The lack of harmful effects observed in chronic intermittent hypoxia in ageing (Quintero et al .…”

“…; Quintero et al . ) does not mean hypoventilation, since it is well known that ageing is accompanied by a decrease in whole body O 2 consumption (Cerveri et al . ; Chan & Welsh, ).…”

“…; Quintero et al . ), demonstrating that the CBs of aged animals are less functional. Consistent with these findings it was found in humans that hypoxic chemosensitivity decreased with age (Peterson et al .…”

Clinical physiology and sleep: insights from the European Respiratory Society Congress 2017

“…In this context, Quintero et al have also shown that age protects from the harmful effects of CIH (13). Since OSA is clinically less conspicuous in aged patients, they compared CIH effects in young (3-4 months) and aged (22-24 months) rats.…”