alpha(2A)-Adrenoceptor mediated tachypnea in awake goats

To further elucidate the role of alpha (2)-adrenoceptors (alpha (2)-ARs) in the control of respiratory rhythm we examined the ventilatory effects of g uanfacine (a preferentially selective alpha (2A)-AR agonist) and clonidine (a non-selective alpha (2)-AR agonist) in awake adult goats. Systemic admin istration of guanfacine in cumulative doses (20 mug/kg; 140-180 mug/kg tota l cumulative dose) increased breathing in all animals in a dose-dependent m anner. The excitatory effect was entirely mediated by increases in respirat ory frequency. The magnitude of the guanfacine-induced tachypnea was simila r to that produced by systemic administration of cumulative doses of clonid ine (1-2 mug/kg; 4-10 mug/kg total cumulative dose) in the same animals stu died on a separate day. Both guanfacine- and clonidine-induced tachypnea wa s reversed by the preferentially selective alpha (2A)-AR antagonist EX82100 2 (2-6 mug/kg IV). Unlike clonidine however, guanfacine administration did not produce slow arrhythmic breathing episodes (irregular TE intervals and central apneas) that are characteristic of alpha (2)-AR stimulation with al pha (2)-AR agonists in the awake goat. The results suggest that alpha (2)-A R agonist-induced ventilatory excitation (tachypnea) requires the activatio n of alpha (2A)-ARs whereas clonidine-induced ventilatory depression (arrhy thmic breathing) requires the activation of an alternate alpha0(2)-AR subty pe (presumably alpha (2C)-ARs). The results further demonstrate that alpha (2)-AR pathways exert,an important influence on respiratory rhythm in the a wake goat. (C) 2001 Elsevier Science B.V. All rights reserved.