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 D2 -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 (C7 -T1 ) of the tachycardic sympathetic tone. The resulting increases in heart rate were evaluated following i.v. blocking doses of antagonists at D2 , D3 and D4 receptors during a continuous i.v. infusion of quinpirole (an agonist at D2 -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 (D2 ), SB-277011-A (D3 ) or L-745,870 (D4 ).
Conclusion: These findings in diabetic pithed rats imply that: (i) the cardiac sympathetic inhibition by quinpirole involves activation of D2/3/4 dopamine receptors; and (ii) there is a differential stimulation of these receptors compared to normoglycemic rats. These D2/3/4 receptor subtypes could be a novel drug target for the therapy of typical cardiac complications of diabetes.
Keywords: Gi/o-protein coupled receptor subtypes; cardiac sympathetic tone; diabetes, dopamine D2-like receptors; pithed rat.
© 2022 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.