Streptozotocin-induced diabetes in rats modifies the role D , D and D dopamine receptors play in cardiac sympathetic inhibition.

BACKGROUND

Diabetes mellitus is associated with abnormalities in peripheral/central catecholaminergic systems, including changes in catecholamine levels and receptor expression.

OBJECTIVE

Since quinpirole-induced cardiac sympathetic inhibition is greater in diabetic than in normoglycemic rats, this study pharmacologically investigated the dopamine D -like receptor subtypes that mediate cardiac sympathetic inhibition in diabetic (streptozotocin [STZ]-pretreated) pithed rats.

METHODS

Fifty male Wistar rats were pretreated with STZ, pithed and conditioned for spinal stimulation (C -T ) of the tachycardic sympathetic tone. The resulting increases in heart rate were evaluated following i.v. blocking doses of antagonists at D , D and D receptors during a continuous i.v. infusion of quinpirole (an agonist at D -like receptors) or saline (vehicle).

RESULTS

With this experimental approach, the cardiac sympathetic inhibition produced by quinpirole in diabetic rats was: (i) unchanged after administration of vehicles and; (ii) abolished by the antagonists L-741,626 (D ), SB-277011-A (D ) or L-745,870 (D ).

CONCLUSION

These findings in diabetic pithed rats imply that: (i) the cardiac sympathetic inhibition by quinpirole involves activation of D dopamine receptors; and (ii) there is a differential stimulation of these receptors compared to normoglycemic rats. These D receptor subtypes could be a novel drug target for the therapy of typical cardiac complications of diabetes.