Effects of pergolide, a dopamine receptor agonist, and clonidine on cardiovascular responses evoked by activation of peripheral sympathetic outflow in rats.
In pentobarbital anesthetized rats, pergolide (10.0 micrograms/kg, i.v.) and clonidine (3.0 micrograms/kg, i.v.) produced similar significant decreases in heart rate and carotid artery pressure. Sulpiride (0.3 mg/kg, i.v.) did not change the effects of clonidine but inhibited entirely the hypotension and partly the bradycardia produced by pergolide. However, yohimbine (0.4 mg/kg) antagonized the cardiovascular effects of clonidine and reduced the bradycardia produced by pergolide. In pithed rats with an experimental, submaximal tachycardia evoked by sustained electrical stimulation of the thoracic sympathetic outflow pergolide and clonidine decreased heart rate. This effect was antagonized by yohimbine (0.1 mg/kg, i.v.) but by not sulpiride (0.3 mg/kg, i.v.). In adrenalectomized, propranolol pretreated pithed rats the pressor responses to 15 sec periods of electrical stimulation of the entire spinal cord were depressed only by pergolide. This effect was blocked by sulpiride. These findings indicate that in the pithed rat the inhibition of neural sympathetic tachycardia by clonidine and pergolide is mediated by stimulation of cardiac presynaptic alpha 2-adrenoceptors. However, only pergolide decreased significantly the pressor responses evoked by electrical stimulation of the peripheral sympathetic outflow and this effect resulted from activation of dopamine receptors located on postganglionic sympathetic neurons innervating resistance blood vessels. Thus, vascular presynaptic alpha 2-adrenoceptors do not appear to contribute to the significant hypotensive effect exerted by 3.0 micrograms/kg, i.v. clonidine in intact rats. Finally, it is suggested that neuronal dopamine receptors might be considered potential target sites for novel peripherally acting antihypertensive agents.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology*; D004558:Electric Stimulation; D004837:Epinephrine / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D010479:Pergolide; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013116:Spinal Cord / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects*
D004873:Ergolines; D011954:Receptors, Dopamine; D010479:Pergolide; D003000:Clonidine; D004837:Epinephrine