Age protects from harmful effects produced by chronic intermittent hypoxia

M. Quintero, E. Olea, S. V. Conde, A. Obeso, T. Gallego-Martin, C. Gonzalez, J. M. Monserrat, A. Gómez-Niño, S. Yubero, T. Agapito

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1773-1790
Number of pages18
JournalJournal Of Physiology-London
Volume594
Issue number6
DOIs
Publication statusPublished - 15 Mar 2016

Keywords

  • OBSTRUCTIVE SLEEP-APNEA
  • RAT CAROTID-BODY
  • BLOOD-PRESSURE
  • MITOCHONDRIAL ACONITASE
  • CARDIOVASCULAR-DISEASE
  • INDUCIBLE FACTORS
  • EPISODIC HYPOXIA
  • OXIDATIVE STRESS
  • JUVENILE RATS
  • OXYGEN

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