Hypotensive actions of ketanserin in dogs: involvement of a centrally mediated inhibition of sympathetic vascular tone.
The intravenous (i.v.) administration of ketanserin (0.1-0.4 mg/kg) produced immediate and sustained decreases in systemic blood pressure and heart rate in pentobarbitone-anaesthetized dogs. These doses of ketanserin did not inhibit common carotid vasoconstrictor responses to intraarterial (i.a.) noradrenaline, pre-ganglionic stimulation of the sectioned cervical sympathetic nerve, or i.v. nicotine, thus the effects of ketanserin are not due to blockade of vascular alpha-adrenoceptors, adrenergic neurone blockade, or ganglionic blockade. Systemic pressor responses to i.v. nicotine, which produces sympathetic activation by both central and ganglionic stimulating actions, and to common carotid artery occlusion, were inhibited by 0.1-0.4 mg/kg of ketanserin i.v. These results suggest that in the anaesthetized dog, the hypotensive action of ketanserin involves a centrally mediated inhibition of sympathetic tone. Peripheral vascular 5-HT2 receptor blockade does not appear to be responsible for the hypotensive effect of ketanserin in this model, although this does not preclude the involvement of such a mechanism in its clinical antihypertensive action.
Phillips
C A
CA
Mylecharane
E J
EJ
Markus
J K
JK
Shaw
J
J
D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007650:Ketanserin; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects*
D000959:Antihypertensive Agents; D006584:Hexamethonium Compounds; D010880:Piperidines; D018738:Hexamethonium; D008464:Mecamylamine; D009538:Nicotine; D007650:Ketanserin