Involvement of central dopamine receptors in the hypotensive action of pergolide

Abstract

The involvement of central dopamine receptors in the hypotensive action of the dopaminergic ergoline, pergolide was determined in anesthetized rats. Intravenous (i.v.) or intracerebroventricular (i.v.t.) administration of pergolide (12.5, 25 and 50 micrograms/kg) produced dose-dependent decreases in blood pressure. The magnitude of hypotension seen following either i.v. or i.v.t. administration of pergolide was similar. However, while both sulpiride (1 mg/kg, i.v.) as well as phentolamine (1 mg/kg, i.v.) antagonized the hypotensive action of i.v. pergolide, only sulpiride (1 mg/kg, i.v.t.) was able to antagonize the hypotension seen following i.v.t. administration of pergolide. Phentolamine (1 mg/kg, i.v.t.) did not alter the central hypotensive action of pergolide. In a separate group of rats, clonidine (25 micrograms/kg, i.v.t.) also produced a decrease in blood pressure. While phentolamine (i.v.t.) antagonized the central hypotensive action of clonidine, sulpiride (i.v.t.) did not have any effect on the action of clonidine. These results show that selective activation of central dopamine receptors was responsible for the hypotensive action of centrally-administered pergolide. In a separate group of rats greater splanchnic sympathetic nerve activity was measured. Intravenous pergolide produced similar hypotensive response as seen in previous groups, and this was accompanied by a concomitant decrease in the sympathetic nerve activity. The maximum fall in blood pressure (26 +/- 6 mm Hg) was correlated with a 40% reduction in sympathetic nerve activity. The return of blood pressure to control levels occurred after 60-70 min and was also associated with the return of sympathetic nerve activity to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of pramipexole with and without domperidone co‐administration on alertness, autonomic, and endocrine functions in healthy volunteers

“…Indeed, it has been reported that dopamine receptor agonists may cause orthostatic hypotension and subjective dizziness [8–12, 14, 46]. This propensity of these drugs is consistent with a reduction in sympathetic activity which may be caused by central [47, 49, 50] and/or peripheral [51–53] mechanisms. Although the location of the central dopamine receptors mediating the sympatholytic effect of dopamine receptor agonists has not been established, it is likely that the VTA is involved since there is evidence that activation of the VTA results in an increase in BP in experimental animals [54].…”

Decrease in hypothalamic epinephrine concentration and other neurochemical changes produced by quinpirole, a dopamine agonist, in rats

“…The increased MHPG sulfate/norepinephrine concentration ratio suggests norepinephrine release may be increased as well. Whether these neurochemical changes are related to functional effects of dopamine agonists such as decreased blood pressure (Jadhav et al, 1983) and increased serum corticosterone concentration is presently unknown, but there have been suggestions that epinephrine neurons can modulate both blood pressure (Saavedra et al, 1976) and corticotrophin-releasing factor secretion (Mez~ et al, 1984) in rats.…”