Streptozotocin‐induced diabetes in rats modifies the role D2, D3 and D4 dopamine receptors play in cardiac sympathetic inhibition

• Published in: Basic & clinical pharmacology & toxicology Vol. 131; no. 4; pp. 262 - 269
• Main Authors: Rivera‐Mancilla, Eduardo, Altamirano‐Espinoza, Alain H., Manrique‐Maldonado, Guadalupe, Villanueva‐Castillo, Belinda, Villalón, Carlos M.
• Format: Journal Article
• Language: English
• Published: Oxford Wiley Subscription Services, Inc 01-10-2022
• Subjects: Abnormalities; Antagonists; cardiac sympathetic tone; Catecholamine; Catecholamines; Complications; Diabetes; Diabetes mellitus; diabetes, dopamine D2‐like receptors; Dopamine; Dopamine D2 receptors; Dopamine D3 receptors; Dopamine D4 receptors; Gi/o‐protein coupled receptor subtypes; Heart rate; pithed rat; Quinpirole; Receptors; Rodents; Stimulation; Streptozocin; Sympathetic nervous system; Therapeutic targets
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/bcpt.13774

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.