Heart rate lowering effects of dihydroergotamine in rats

Dihydroergotamine (10-100 micrograms/kg i.v.) decreased heart rate in pentobarbital anesthetized rats. This bradycardia was reduced but not blocked by guanethidine, yohimbine, propranolol, atropine, haloperidol, sulpiride, bivagotomy or pithing. In the pithed rat, dihydroergotamine failed to affect either the bradycardia produced by electrical stimulation of the vagus or the cardioacceleration evoked by i.v. isoproterenol, tyramine or aminophylline. The increase in heart rate elicited by electrical stimulation of the spinal cord was reduced by dihydroergotamine, this effect being blocked by yohimbine. In conclusion, in the rat, the main mechanism by which dihydroergotamine induces bradycardia involves stimulation of central and peripheral alpha 2-adrenoceptors. Via an action on these receptors, dihydroergotamine can inhibit the sympathetic outflow and enhance efferent vagal activity. This bradycardia may also reinforced by stimulation of central dopaminergic receptors and direct myocardial depression.