Pharmacological, hemodynamic and biochemical mechanisms involved in the blood pressure lowering effects of pergolide, in normotensive and hypertensive dogs.
In pentobarbital-anesthetized normotensive dogs, clonidine (20.0 micrograms/kg i.v.), in contrast to pergolide (30.0 micrograms/kg i.v.), reduced significantly both aortic blood pressure and plasma concentration of norepinephrine. However, in dogs that had been made hypertensive by sectioning the vagi and carotid sinus nerves, pergolide, like clonidine, lowered the blood pressure and plasma concentrations of epinephrine and norepinephrine that were enhanced markedly by deafferentation. Furthermore, in this preparation pergolide decreased the calculated resistance in vascular regions supplied by the upper abdominal aorta and the innervated femoral and renal arteries, but it increased vascular resistance in the denervated hind leg. Pergolide (1.0 microgram/kg) injected intracisternally (i.c.m.) induced a fall in blood pressure of comparable magnitude to that produced by a 30 times higher i.v. dose. Intravenously and i.c.m. administered pergolide lowered blood pressure by acting at distinct anatomical sites inasmuch as i.v. sulpiride blocked the effects of i.v. but not i.c.m. pergolide. The combination of sulpiride plus yohimbine injected i.c.m. was necessary to abolish the decrease in blood pressure evoked by i.c.m. pergolide. In atropinized spinal dogs, i.v. pergolide inhibited the vasoconstriction elicited by electrical stimulation of the lumbar sympathetic chain, an effect which was antagonized by sulpiride. Similarly, pergolide (30.0 micrograms/kg i.v.) like clonidine, reduced the heart rate and coronary venous plasma norepinephrine concentration raised by sustained electrical stimulation of the cardioaccelerator nerve. Sulpiride, but not phentolamine, antagonized this pergolide-induced inhibition of sympathetic nerve function. In chlorisondamine-pretreated dogs, pergolide produced a transient pressor response due to stimulation of postsynaptic vascular alpha-2 adrenoceptors. In conclusion, the failure of i.v. pergolide to decrease aortic blood pressure in pentobarbital-anesthetized normotensive dogs is presumably due to the inability of pergolide to produce a significant inhibition of the vascular sympathetic tone in this preparation. However, in neurogenic hypertensive dogs which are characterized by an elevated level of sympathetic drive, i.v. pergolide reduced blood pressure and aortic plasma norepinephrine concentration. These effects of pergolide are compatible with a DA-2 dopamine receptor stimulation on peripheral sympathetic nerve fibers. In contrast, the antihypertensive effects of i.c.m. pergolide would appear to be mediated by both alpha-2 adrenoceptors and DA-2 dopamine receptors located within the central nervous system.
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D003714:Denervation; D004285:Dogs; D004558:Electric Stimulation; D004873:Ergolines / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology; D010479:Pergolide; D011954:Receptors, Dopamine / Q000032:analysis / Q000187:drug effects; D017448:Receptors, Dopamine D2; D013469:Sulpiride / Q000494:pharmacology; D014628:Vagotomy; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D004873:Ergolines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D010479:Pergolide; D013469:Sulpiride; D003000:Clonidine; D009638:Norepinephrine