title: Hypercapnia-induced long-term depression of respiratory activity requires alpha2-adrenergic receptors.
abstract: We investigated the effects of repeated hypercapnic episodes (inspired CO2 fraction = 0.10) on posthypercapnic respiratory nerve discharge. Anesthetized (urethan), vagotomized, and artificially ventilated rats were presented with three consecutive 5-min episodes of hyperoxic hypercapnia, separated by 5 min of hyperoxic normocapnia (inspired O2 fraction = 0.5). Respiratory nerve discharge and blood gases were recorded before and 30 and 60 min after the final hypercapnic episode. Posthypercapnia, arterial PCO2 was maintained within 1 Torr of initial baseline values. Integrated phrenic and hypoglossal burst amplitudes decreased posthypercapnia by up to 46 +/- 17 and 55 +/- 13% of baseline values, respectively, and remained reduced for at least 1 h [long-term depression (LTD)]. The protocol was repeated in rats pretreated with the alpha2-adrenergic antagonists yohimbine HCl (0.5 mg/kg; n = 7) or 2-[2-(2-methoxy-1,4-benzodioanyl)]imidazoline (RX-821002) HCl (0.25 mg/kg; n = 3). Both drugs attenuated LTD in the phrenic and hypoglossal neurograms. Results indicate that episodic hypercapnia elicits a yohimbine- and RX-821002-sensitive LTD of respiratory nerve activity in rats, suggesting that LTD requires alpha2-receptor activation.
authors.affiliation: Department of Comparative Biosciences and Center for Neuroscience, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors.forename: K B
authors.initials: KB
authors.lastname: Bach
authors.forename: G S
authors.initials: GS
authors.lastname: Mitchell
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D006935:Hypercapnia / Q000503:physiopathology*; D007002:Hypoglossal Nerve / Q000187:drug effects / Q000502:physiology; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*; D014628:Vagotomy; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018341:Receptors, Adrenergic, alpha-2; D002245:Carbon Dioxide; D015016:Yohimbine; C058525:2-methoxyidazoxan; D009638:Norepinephrine; D019329:Idazoxan