Post-hypoxia frequency decline in rats:: sensitivity to repeated hypoxia and α2-adrenoreceptor antagonism

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 alpha(2)-adrenoreceptor antagonism. Anesthetized (urethane), artificially ventilated (F(IO2) = 0.50) and vagotomized rats were presented with two or three, 5 min episodes of isocapnic hypoxia (F(IO2) =o.11) separated by 30 min of control, hyperoxic conditions. Phrenic nerve discharge, end-tidal CO, 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 alpha(2)-receptor antagonist, RX821002 HCl (2-[2-(2-Methoxy-1,4-benzodioxanyl)l 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 alpha(2) adrenoreceptor activation plays a role in its underlying mechanism. (C) 1999 Elsevier Science B.V. All rights reserved.