α_2A-Adrenoceptor mediated tachypnea in awake goats

To further elucidate the role of α₂-adrenoceptors (α₂-ARs) in the control of respiratory rhythm we examined the ventilatory effects of guanfacine (a preferentially selective α_2A-AR agonist) and clonidine (a non-selective α₂-AR agonist) in awake adult goats. Systemic administration of guanfacine in cumulative doses (20 μg/kg; 140-180 μg/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 μg/kg; 4-10 μg/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 α_2A-AR antagonist RX821002 (2-6 μg/kg IV). Unlike clonidine however, guanfacine administration did not produce slow arrhythmic breathing episodes (irregular TE intervals and central apneas) that are characteristic of α₂-AR stimulation with α₂-AR agonists in the awake goat. The results suggest that α₂-AR agonist-induced ventilatory excitation (tachypnea) requires the activation of α_2A-ARs whereas clonidine-induced ventilatory depression (arrhythmic breathing) requires the activation of an alternate α₂-AR subtype (presumably α_2C-ARs). The results further demonstrate that α₂-AR pathways exert an important influence on respiratory rhythm in the awake goat.