Effects of glucocorticoid on cardiac chronotropic responsiveness in cirrhotic rats: A possible role for dopamine receptors

Articles in Press

Document Type : Original Article

Authors

1 Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

2 Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA

4 Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan

5 Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, USA

10.22038/ijbms.2026.91247.19739

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. 

Keywords

Main Subjects

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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 05 May 2026

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