Cardiovascular effects of ketanserin on normotensive rats in vivo and in vitro.
In this work, we report for first time that: (1) low doses of ketanserin (0.2 mg/kg) produce a transient hypotensive response in anaesthetized rats, which is basically due to the blockade of 5-hydroxytryptamine (2A) (5-HT)2A receptors, whereas high doses (1 mg/kg) of ketanserin cause a sustained hypotension also mediated by the blockage of alpha1-adrenergic receptors; (2) the in vitro vasorelaxant action of high concentrations of ketanserin (>10 microM) involves Ca2+ antagonism, which may also be responsible, at least in part, for the inhibition of high-K+-induced 45Ca2+ uptake, the inhibition of Ca2+-induced contractions in initially Ca2+-free high-K+ medium, and the negative chronotropic effects on isolated atria. This Ca2+ antagonistic activity does not seem to contribute to the in vivo cardiovascular effects of ketanserin at therapeutic doses.
Orallo
F
F
Departamento de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782, Santiago de Compostela, Spain.
Rosa
E
E
García-Ferreiro
T
T
Campos-Toimil
M
M
Cadavid
M I
MI
Loza
M I
MI
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*
D012702:Serotonin Antagonists; D012701:Serotonin; D007650:Ketanserin; D002118:Calcium; D009638:Norepinephrine