HYPERCAPNIA-INDUCED LONG-TERM DEPRESSION OF RESPIRATORY ACTIVITY REQUIRES ALPHA(2)-ADRENERGIC RECEPTORS

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 hype rcapnia, separated by 5 min of hyperoxic normocapnia (inspired O-2 fra ction = 0.5). Respiratory nerve discharge and blood gases were recorde d before and 30 and 60 min after the final hypercapnic episode. Posthy percapnia, arterial P-CO2 was maintained within 1 Torr of initial base line values. Integrated phrenic and hypoglossal burst amplitudes decre ased posthypercapnia by up to 46 +/- 17 and 55 +/- 13% of baseline val ues, respectively, and remained reduced for at least 1 h [long-term de pression (LTD)]. The protocol was repeated in rats pretreated with the az-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 neurogr ams. Results indicate that episodic hypercapnia elicits a yohimbine- a nd RX-821002-sensitive LTD of respiratory nerve activity in rats, sugg esting that LTD requires alpha(2)-receptor activation.