title: Post-hypoxia frequency decline in rats: sensitivity to repeated hypoxia and alpha2-adrenoreceptor antagonism.
abstract: We tested the hypothesis that the post-hypoxia frequency decline of phrenic nerve activity following brief, isocapnic hypoxic episodes in rats is diminished by prior hypoxic episodes and alpha2-adrenoreceptor antagonism. Anesthetized (urethane), artificially ventilated (FIO2=0.50) and vagotomized rats were presented with two or three, 5 min episodes of isocapnic hypoxia (FIO2 approximately 0.11), separated by 30 min of control, hyperoxic conditions. Phrenic nerve discharge, end-tidal CO2, and arterial blood gases were measured before during and after hypoxia. The average maximum frequency decline, measured 5 min after the first hypoxic episode, was 26+/-7 bursts/min below pre-hypoxic baseline values (a 70+/-16% decrease). By 30 min post-hypoxia, frequency had returned to baseline. Two groups of rats were then administered either: (1) saline (sham) or (2) the alpha2-receptor antagonist, RX821002 HCl (2-[2-(2-Methoxy-1,4-benzodioxanyl)] imidazoline hydrochloride; 0.25 mg/kg, i.v.). Isocapnic hypoxia was repeated 10 min later. In sham rats, the post-hypoxia frequency decline (PHFD) was significantly attenuated relative to the initial (control) response. However, PHFD was attenuated significantly more in RX821002-treated vs. sham rats (-3+/-3 bursts/min vs. -12+/-4 bursts/min @ 5 min post hypoxia for RX821002 and sham-treated, respectively; p<0.05). We conclude that the magnitude of PHFD is dependent on the prior history of hypoxia and that alpha2 adrenoreceptor activation plays a role in its underlying mechanism.
authors.affiliation: Department of Comparative Biosciences and Center for Neuroscience, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Drive West, Madison, WI, 53706, USA.bachk@svm.vetmed.wisc.edu
authors.forename: K B
authors.initials: KB
authors.lastname: Bach
authors.forename: R
authors.initials: R
authors.lastname: Kinkead
authors.forename: G S
authors.initials: GS
authors.lastname: Mitchell
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D000860:Hypoxia / Q000188:drug therapy*; D008297:Male; D010791:Phrenic Nerve / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence
chemical_list: D000319:Adrenergic beta-Antagonists; D002245:Carbon Dioxide