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.
D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004285:Dogs; D004294:Domperidone / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009541:Nictitating Membrane / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011954:Receptors, Dopamine / Q000187:drug effects*; D012079:Renal Circulation / Q000187:drug effects; D013045:Species Specificity
D000959:Antihypertensive Agents; D004873:Ergolines; D011954:Receptors, Dopamine; D010868:Pimozide; D004294:Domperidone; C039327:cianergoline; D011433:Propranolol; D006220:Haloperidol; D007545:Isoproterenol; D009638:Norepinephrine; D007213:Indomethacin; D010646:Phentolamine