Central and peripheral dopaminergic mechanisms in the cardiovascular actions of pergolide in neurogenic hypertensive dogs.
The cardiovascular actions of the dopaminergic ergoline, pergolide were examined in pentobarbital-anesthetized dogs. When administered intravenously (i.v.) to dogs made hypertensive by sino-aortic deafferentation, pergolide produced a sustained reduction in blood pressure, dilatation of the hindlimb vasculature and bradycardia. The antihypertensive action of pergolide in neurogenic hypertensive dogs was converted into a pressor action when it was given to dogs pretreated with i.v. sulpiride or hexamethonium plus atropine. Pergolide caused significant impairment of renal vasoconstriction elicited during stimulation of renal sympathetic nerves but not that caused by exogenous norepinephrine. The inhibitory action of pergolide on renal sympathetic nerve function was antagonized by sulpiride suggesting that pergolide activated presynaptic dopamine receptors. Direct administration of pergolide within the central nervous system via the cisterna magna (i.c.) to normotensive dogs also resulted in hypotension, bradycardia and iliac vasodilatation. The central actions of pergolide were prevented by sulpiride (i.c.) but not by yohimbine (i.c.), which indicates that specific activation of central dopamine receptors was responsible for these actions of pergolide. The antihypertensive, bradycardic and iliac vasodilatory actions of i.v. pergolide in neurogenic hypertensive dogs were significantly attenuated by i.c. sulpiride. It was determined that while this dose of sulpiride antagonized central dopamine receptors, it did not antagonize peripheral presynaptic dopamine receptors. These results suggest that pergolide exerts antihypertensive and bradycardic actions via simultaneous stimulation of dopamine receptors in the brain and on postganglionic sympathetic neurons. While presynaptic dopamine receptor activation contributes to the blood pressure lowering action of pergolide, stimulation of central dopamine receptors appears to be the dominant mechanism by which pergolide elicits the observed antihypertensive and bradycardic effects. Pergolide appears to lower blood pressure by a novel mechanism of action and may offer an additional therapeutic approach for the treatment of hypertension.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects*; D004285:Dogs; D004873:Ergolines / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010479:Pergolide; D010525:Peripheral Nerves / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects*; D012079:Renal Circulation / Q000187:drug effects; D013469:Sulpiride / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D002317:Cardiovascular Agents; D004873:Ergolines; D011954:Receptors, Dopamine; D010479:Pergolide; D013469:Sulpiride; D009638:Norepinephrine