Evidence for a central component to the hypotensive action of ketanserin in the dog.
The mechanisms responsible for the hypotensive action of ketanserin are controversial. Vascular 5-HT2-receptor blockade, resulting in inhibition of serotonin-induced vasoconstriction and amplification of other vasoconstrictors, has been suggested by some investigators, but others have concluded that vascular alpha-adrenoceptor blockade is responsible. In our experiments using pentobarbitone-anaesthetized dogs, ketanserin (0.1-0.4 mg/kg i.v.) produced immediate and sustained falls in systemic arterial blood pressure and vascular resistance in the common carotid and femoral arterial circulations. Constrictor responses to noradrenaline in these circulations were unaffected by 0.1-0.4 mg/kg i.v. of ketanserin; alpha-adrenoceptor blockade was only produced by higher doses (1-4 mg/kg i.v.). Constrictor responses in the common carotid circulation to preganglionic cervical sympathetic nerve stimulation and to nicotine were not inhibited by 0.1-0.4 mg/kg of ketanserin. The systemic pressor responses to nicotine and common carotid artery occlusion, however, were reduced by these doses of ketanserin. These results suggest that alpha-adrenoceptor blockade is not responsible for the hypotensive action of 0.1-0.4 mg/kg of ketanserin, and that a centrally mediated inhibition of sympathetic nerve activity is involved.
E J
EJ
Mylecharane
C A
CA
Phillips
J K
JK
Markus
J
J
Shaw
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004285:Dogs; D005730:Ganglionic Blockers / Q000494:pharmacology; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007650:Ketanserin; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D000959:Antihypertensive Agents; D005730:Ganglionic Blockers; D006584:Hexamethonium Compounds; D010880:Piperidines; D008464:Mecamylamine; D009538:Nicotine; D007650:Ketanserin; D009638:Norepinephrine