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.
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 / Q000008:administration & dosage / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006041:Goats; D016316:Guanfacine / Q000008:administration & dosage / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D010507:Periodicity; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology*; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D018341:Receptors, Adrenergic, alpha-2; D016316:Guanfacine; C058525:2-methoxyidazoxan; D003000:Clonidine; D019329:Idazoxan