Effects of Glucocorticoid on Cardiac Chronotropic Responsiveness in Cirrhotic Rats: A Possible Role for Dopamine Receptors Publisher



Zeini M S ; Niaz Q ; Saeedi Saravi S S ; Dehpour A R ; Jazaeri F
Source: Iranian Journal of Basic Medical Sciences Published:2026

Abstract

Objective(s): Cirrhosis causes chronotropic dysfunction by weakening the β-adrenergic receptor (β-AR) signaling pathway in cirrhotic cardiomyopathy (CCM). Downstream signaling of glucocorticoids and dopamine receptors influences the β-AR pathway. Thus, the effects of glucocorticoids on chronotropic incompetence and the possible involved pathways were investigated in this experiment. Materials and Methods: Bile duct ligation (BDL) surgery was performed on Wistar rats to induce cirrhosis. Four weeks after BDL or sham surgery, the subjects were given an intramuscular injection of either saline (NS) or dexamethasone (dexa) (2.2 mg/kg/day) for three consecutive days. In vivo, chronotropic responsiveness to isoproterenol and QTc interval were evaluated by electrocardiogram (ECG). Real-time polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were performed to determine the effectiveness of dexa on dopamine D1, D2 receptors, and GNAL mRNA expression. Moreover, the tumor necrosis factor-alpha (TNF-α) and interleukin‐1beta (IL-1β) levels in rats’ hearts were assessed. Results: Dexa treatment reduced the prolonged QT intervals in cirrhosis. It also dedcreasd spleen weight, as well as TNF-α levels, which are increased in cirrhosis. Moreover, dexa increased D1 protein expression in IHC. Conclusion: Dexa effectively improved cirrotic heart by improving QT intervales and increasing spleen weight, reducing a pro-inflammatory cytokine, and up-regulateing D1 receptor protein expression. © 2026. This work is openly licensed via CC BY 4.0. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.