Ventilatory effects of alpha2-adrenoceptor blockade in awake goats

We sought to determine the extent to which alpha2-adrenoceptor (alpha2-AR) pathways exert a tonic influence on respiratory rhythm under normal physiological conditions. The ventilatory effects of alpha2-AR blockade with SKF-86466 were examined in awake adult goats. The antagonist effect of SKF-86466 at alpha(2)-ARs was evident both as a reversal of the ventilatory disturbances produced by the alpha2-AR agonist clonidine (5 microg/kg IV) and as a rightward shift in the potency of the agonist-evoked response after SKF-86466 pretreatment. Systemic administration of SKF-86466 in cumulative doses (25-250 microg/kg) or as a single bolus injection (500 microg/kg) produced dose-dependent increases in breathing in all animals. The excitatory effect was primarily mediated by increases in respiratory frequency that persisted for at least 120 min after injection (500 microg/kg). The time course and magnitude of the ventilatory response to SKF-86466 was similar in carotid body denervated animals. The ventilatory response to isocapnic hypoxia but not normoxic hypercapnia was significantly elevated after SKF-86466 administration (500 microg/kg). SKF-86466 (25-1000 microg/kg) produced dose-dependent increases in heart rate in all animals but did not significantly change mean arterial blood pressure at any dose. The results demonstrate that alpha2-AR pathways exert a tonic inhibitory influence on respiratory rhythm in the awake goat.