Alpha2A-adrenoceptor mediated tachypnea in awake goats

To further elucidate the role of alpha2-adrenoceptors (alpha2-ARs) in the control of respiratory rhythm we examined the ventilatory effects of guanfacine (a preferentially selective alpha2A-AR agonist) and clonidine (a non-selective alpha2-AR agonist) in awake adult goats. Systemic administration of guanfacine in cumulative doses (20 microg/kg; 140-180 microg/kg total cumulative dose) increased breathing in all animals in a dose-dependent manner. The excitatory effect was entirely mediated by increases in respiratory frequency. The magnitude of the guanfacine-induced tachypnea was similar to that produced by systemic administration of cumulative doses of clonidine (1-2 microg/kg; 4-10 microg/kg total cumulative dose) in the same animals studied on a separate day. Both guanfacine- and clonidine-induced tachypnea was reversed by the preferentially selective alpha2A-AR antagonist RX821002 (2-6 microg/kg IV). Unlike clonidine however, guanfacine administration did not produce slow arrhythmic breathing episodes (irregular TE intervals and central apneas) that are characteristic of alpha2-AR stimulation with alpha2-AR agonists in the awake goat. The results suggest that alpha2-AR agonist-induced ventilatory excitation (tachypnea) requires the activation of alpha2A-ARs whereas clonidine-induced ventilatory depression (arrhythmic breathing) requires the activation of an alternate alpha2-AR subtype (presumably alpha2C-ARs). The results further demonstrate that alpha2-AR pathways exert an important influence on respiratory rhythm in the awake goat.