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Testosterone induces higher carotid body response to hypoxia in older adult male rats
Author(s) -
Kinkead Richard,
Janes Tara Adele,
Soliz Jorge
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02944
Subject(s) - carotid body , endocrinology , medicine , testosterone (patch) , hypoxia (environmental) , hypoxic ventilatory response , ageing , in vivo , respiratory system , chemistry , biology , stimulation , oxygen , microbiology and biotechnology , organic chemistry
Excessive carotid body responsiveness to chemical stimuli contributes to respiratory instability and apneas during sleep. In hypogonadal men, testosterone supplementation increases the risk of sleep‐disordered breathing; however, the site of action is unknown. The present study tested the hypothesis that exposure to elevated levels of testosterone potentiates the carotid body’s response to hypoxia. Because testosterone levels decline with age, we also determined whether these effects are age‐dependent. To do so, carotid bodies were isolated ex vivo from young (70 days old) and aging (185 days old) male Sprague‐Dawley rats. Isolated organs were maintained in oxygenated Tyrode solution (95% O 2 ; 5% CO 2 ) in the presence of testosterone (5 nM) or vehicle (<0.001% DMSO) for 90–120 min. Preparations were then mounted in the recording chamber and a suction electrode was placed on the carotid sinus nerve to record activity (# of impulses/sec). Activity was recorded at rest and during exposure to hypoxia (0% O 2 , 5% CO 2 , 95% N 2 ; 15 min). Basal carotid body activity did not differ between age groups; however, the responses to both stimuli were greater in young rats. Testosterone exposure augmented the responses to hypoxia in aging rats only. In vivo experiments performed on anesthetised rats show that testosterone injection (2 mg/kg) 30 min prior hypoxic exposure (12%O 2 ; 20 min) potentiates the hypoxic ventilatory response in an age‐dependent fashion. We conclude that age‐dependent potentiation of the carotid body’s O 2 chemosensitivity by testosterone may lead to ventilatory adjustments that exceed the organism’s need. In aging animals, this may predispose to respiratory instability and apnea during sleep. Support or Funding Information Supported by a discovery grant from the Natural Sciences and Engineering Research Council of Canada (RK). Dr Janes was supported by a scholarship from the Réseau en Recherche Respiratoire du Québec.