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.