Streptozotocin‐induced diabetes in rats modifies the role D2, D3and D4dopamine receptors play in cardiac sympathetic inhibition

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Abstract Background Diabetes mellitusis 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, D3and D4receptors 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 D2/3/4dopamine receptors; and (ii) there is a differential stimulation of these receptors compared to normoglycemic rats. These D2/3/4receptor subtypes could be a novel drug target for the therapy of typical cardiac complications of diabetes.

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