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 α₁-adrenergic receptors; (2) the in vitro vasorelaxant action of high concentrations of ketanserin (>10 μM) 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.