Involvement of peripheral dopamine receptors in the antihypertensive effect of a new ergoline derivative (355/1057).

Oral administration of a new ergoline derivative (355/1057) produced a sustained arterial hypotension in conscious SHR rats. This effect was inhibited by the centrally acting DA blockers haloperidol and pimozide and by domperidone, a DA antagonist that does not cross the blood brain barrier. On the other hand it was unaffected by alpha- and beta-adrenoceptor blockers or by indomethacin. Moreover, the hypertension induced by 355/1057 in pithed SHR rats was reversed to hypotension when its alpha-adrenoceptor stimulant activity was inhibited by yohimbine. In anesthetized dogs the hypotensive activity of 355/1057 was abolished by pimozide but not by propranolol. In anesthetized cats, pretreatment with haloperidol prevented both the hypotensive activity of 355/1057 and its inhibitory effect on sympathetic nerve activity. These overall data suggest that 355/1057 lowers blood pressure in different species mainly by stimulating peripheral dopamine receptors.