Post-hypoxia frequency decline in rats: sensitivity to repeated hypoxia and α2-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 α2-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≈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 α2-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 α2 adrenoreceptor activation plays a role in its underlying mechanism.