title: Adenosine receptors mediate the hypoxic ventilatory response but not the hypoxic metabolic response in the naked mole rat during acute hypoxia.
abstract: Naked mole rats are the most hypoxia-tolerant mammals identified; however, the mechanisms underlying this tolerance are poorly understood. Using whole-animal plethysmography and open-flow respirometry, we examined the hypoxic metabolic response (HMR), hypoxic ventilatory response (HVR) and hypoxic thermal response in awake, freely behaving naked mole rats exposed to 7% O₂ for 1 h. Metabolic rate and ventilation each reversibly decreased 70% in hypoxia (from 39.6 ± 2.9 to 12.1 ± 0.3 ml O₂ min(-1) kg(-1), and 1412 ± 244 to 417 ± 62 ml min(-1) kg(-1), respectively; p < 0.05), whereas body temperature was unchanged and animals remained awake and active. Subcutaneous injection of the general adenosine receptor antagonist aminophylline (AMP; 100 mg kg(-1), in saline), but not control saline injections, prevented the HVR but had no effect on the HMR. As a result, AMP-treated naked mole rats exhibited extreme hyperventilation in hypoxia. These animals were also less tolerant to hypoxia, and in some cases hypoxia was lethal following AMP injection. We conclude that in naked mole rats (i) hypoxia tolerance is partially dependent on profound hypoxic metabolic and ventilatory responses, which are equal in magnitude but occur independently of thermal changes in hypoxia, and (ii) adenosine receptors mediate the HVR but not the HMR.
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4 pamenter@zoology.ubc.ca.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Pamenter
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
authors.forename: Yvonne A
authors.initials: YA
authors.lastname: Dzal
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.
authors.forename: William K
authors.initials: WK
authors.lastname: Milsom
mesh_terms: D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001481:Basal Metabolism; D001831:Body Temperature / Q000502:physiology; D005260:Female; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D019577:Mole Rats / Q000502:physiology*; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D015656:Respiratory Mechanics / Q000502:physiology; D014851:Wakefulness
chemical_list: D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D000628:Aminophylline
keywords: hypoxic metabolic response; hypoxic ventilatory response; plethysmography; respirometry; thermal response