Action of clonidine on the baroreceptor pathway and medullary sites mediating vagal bradycardia.
In anaesthetized dogs, clonidine (10 mug/kg i.v.) increased the spontaneous firing of the carotid sinus nerve and decreased blood pressure and heart rate. After transection of the spinal cord, clonidine decreased heart rate and this bradycardia was abolished by selective baroreceptor denervation. Clonidine (1 mug/kg) injected into the vertebral artery of anaesthetized dogs, pretreated with a beta-adrenoceptor blocking agent (S 2395: 50 mug/kg i.v.) potentiated the bradycardia induced by stimulation of the carotid sinus nerve but did not change the hypotension and bradycardia produced by stimulation of the nucleus tractus solitarius or of the nucleus ambiguus. In anaesthetized cats with bilateral destruction of nuclei tractus solitarii, clonidine (10 mug/kg i.v.) decreased blood pressure and heart rate. Clonidine (2 mug/kg), injected into the vertebral artery of anaesthetized dogs pretreated with a beta-adrenergic blocking agent (S 2395: 50 mug/kg i.v.) or guanethidine, induced a bradycardia but the discharges of the carotid sinus nerve were not increased. Selective baroreceptor denervation abolished this bradycardia. In conclusion, these experiments provide direct evidence that the central facilitory effect of clonidine on baroreceptor impulses play a role in the bradycardic effect of the drug. This facilitation is likely localized in the nucleus tractus solitarius at the first synapse of baroreceptor fibres. The vagally mediated bradycardia can be explained by an increase in baroreceptor discharges and by the central facilitation of baroreceptor impulses. The site of the hypotensive effect of clonidine did not seem to be localized in the nucleus tractus solitarius.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002346:Carotid Sinus / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology*; D003714:Denervation; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D011311:Pressoreceptors / Q000187:drug effects*; D013116:Spinal Cord / Q000502:physiology; D013153:Splanchnic Nerves / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology*
D003000:Clonidine