Presynaptic dopamine receptor stimulation in the cardiovascular actions of lergotrile

The involvement of dopamine receptors present at different sites in the hypotensive and bradycardic actions of lergotrile was investigated. Intravenous administration of lergotrile to pentobarbital-anesthetized dogs decreased blood pressure, heart rate and renal vascular resistance and increased renal blood flow. These effects were prevented by prior treatment with sulpiride or with hexamethonium plus atropine. When administered to phentolamine-treated animals, lergotrile failed to alter either blood pressure or renal blood flow, but exerted and an enhanced bradycardic effect. Lergotrile significantly inhibited the positive chronotropic and renal vasoconstrictor effects elicited by cardiac and renal sympathetic nerve stimulation, which could be prevented by prior treatment with sulpiride, suggesting that stimulation of presynaptic dopamine receptors was responsible for the inhibition of sympathetic nerve function caused by lergotrile. Administration of lergotrile into the vertebral artery did not produce any cardiovascular changes, whereas i.c.v. lergotrile caused a transient tachycardia followed by a bradycardia of greater magnitude and duration than that seen after i.v. administration. These studies suggest that lergotrile exerts its hypotensive and bradycardiac effects via stimulation of presynaptic dopamine receptors resulting in subsequent inhibition of sympathetic nerve function. Dopamine receptors present in the brain may contribute to the bradycardia, but vascular dopamine receptors do not appear to be involved in the cardiovascular actions of lergotrile.