The acute and chronic antihypertensive effects of ketanserin cannot be explained by blockade of vascular serotonin, type 2, receptors or alpha 1-adrenergic receptors.
The mechanism underlying the antihypertensive effect of acute and chronic administration of ketanserin was investigated in eight hypertensive patients. Intrabrachial artery infusions of serotonin and the selective alpha 1-adrenergic receptor agonist methoxamine were given before and 1 hour after a single oral dose of 20 mg ketanserin and after 4 weeks of treatment with 20 to 40 mg twice daily. Blood pressure was reduced by ketanserin both after the initial dose (p less than 0.01) and after 4 weeks of treatment (p less than 0.01). During placebo, serotonin, 1 ng/kg/min, increased forearm blood flow by 51% +/- 9% (p less than 0.01), whereas the highest dose induced a decrease in flow (-33% +/- 6%; p less than 0.01). Methoxamine elicited a vasoconstriction (p less than 0.001). These effects of serotonin and methoxamine were not influenced by either the initial dose of ketanserin or after 4 weeks of treatment. It is concluded that serotonin cannot be considered a general endogenous pressor agent in these patients. The antihypertensive effects of ketanserin cannot be attributed to either vascular alpha 1-receptor or serotonin, type 2, receptor blockade.
Blauw
G J
GJ
Department of Nephrology, University Hospital, Leiden, The Netherlands.
van Brummelen
P
P
Doorenbos
C J
CJ
van der Velde
E A
EA
van Zwieten
P A
PA
D000328:Adult; D000368:Aged; D004347:Drug Interactions; D005260:Female; D005542:Forearm / Q000098:blood supply; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007261:Infusions, Intra-Arterial; D007650:Ketanserin / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008729:Methoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D012701:Serotonin; D007650:Ketanserin; D008729:Methoxamine