BACKGROUND: One of prominent cardiovascular effects of imipramine is postural hypotension. The present study was to verify whether imipramine has a central hypotensive action and futher to investigate its mechanism of action. METHODS: Rats(male, Sprague-Dawley) weighing 250-300g were anesthetized with pentobarbital sodium(50mg/kg, ip). Imipramine was administered into the left lateral cerebral ventricle. Mean arterial pressure(MAP) and heart rate(HR) were continuously monitored from the right femoral artery. RESULTS: Intracerebroventricular(icv) imipramine(3micromol/kg) caused decrease in MAP without significant alterations in HR, of which safety dose-range was very narrow. 1micromol/kg did not affect MAP and 10micromol/kg caused deaths of animals within 10min. Intravenous infusion of the same dose(3micromol/kg) of imipramine caused only a transient hypotension within 5min. Hexamethonium-treated(1mg/kg/min) rats did not respond to icv imipramine. Regitine pretreatment(2mg/kg, iv) prevented the hypotensive response to icv imipramine. Yohimbine pretreatment(500microg/kg, icv) not only blocked the hypotensive effect, but it caused a transient pressor response to icv imipramine. CONCLUSIONS: These results indicate that imipramine has a separate hypotensive effect which is mediated through central alpha2-adrenoceptors.
Animals ; Blood Pressure ; Cerebral Ventricles ; Femoral Artery ; Heart ; Hypotension ; Hypotension, Orthostatic ; Imipramine* ; Infusions, Intravenous ; Pentobarbital ; Phentolamine ; Rats* ; Yohimbine