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.
O'Halloran
K D
KD
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Drive West, Madison, WI 53706, USA. ken.ohalloran@ucd.ie
Herman
J K
JK
Bisgard
G E
GE
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002344:Carotid Body / Q000502:physiology; D003000:Clonidine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003714:Denervation; D005260:Female; D006041:Goats; D006339:Heart Rate / Q000187:drug effects; D006935:Hypercapnia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D012119:Respiration / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001552:Benzazepines; D003000:Clonidine; C039139:benalfocin