1. Propranolol Alleviates Cardiac Injury After Acute Catecholamine Infusion Through p38-MAPK Pathways.
- Author
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Liu TH, Hsieh RJ, Chen HH, Kuo TJ, Lee JC, and Lu WH
- Subjects
- Animals, Male, Rats, Epinephrine toxicity, Epinephrine administration & dosage, Phosphorylation, Apoptosis drug effects, Disease Models, Animal, Myocardium pathology, Myocardium metabolism, Myocardium enzymology, Catecholamines metabolism, Reactive Oxygen Species metabolism, Propranolol pharmacology, Rats, Sprague-Dawley, p38 Mitogen-Activated Protein Kinases metabolism, Adrenergic beta-Antagonists pharmacology, Adrenergic beta-Antagonists administration & dosage, Heart Failure drug therapy, Heart Failure metabolism, Heart Failure pathology, Heart Failure physiopathology, Heart Failure chemically induced, Norepinephrine metabolism, Fibrosis
- Abstract
Abstract: Hypercatecholaminergic conditions are known to cause heart failure and cardiac fibrosis when severe. Although previous investigations have studied the effects of beta-blockade in experimental models of catecholaminergic states, the detailed benefits of beta-blockade in more realistic models of hyper-adrenergic states were less clear. In this study, we examined acute cardiac changes in rats with hyperacute catecholamine-induced heart failure with and without propranolol treatment. Male Sprague-Dawley rats (n = 12) underwent a 6-hour infusion of epinephrine and norepinephrine alone, with an additional propranolol bolus (1 mg/kg) at hour 1 (n = 6). Cardiac tissues were examined after 6 hours. Cardiac immunohistochemistry revealed significantly decreased expression of phosphorylated p-38 (left ventricle, P = 0.021; right ventricle, P = 0.021), with upregulation of reactive oxidative species and other profibrosis proteins, after catecholamine infusion alone. After 1 propranolol 1 mg/kg bolus, the levels of phosphorylated-p38 returned to levels comparable with sham (left ventricle, P = 0.021; right ventricle, P = 0.043), with additional findings including downregulation of the apoptotic pathway and profibrotic proteins. We conclude that catecholamine-induced heart failure exerts damage through the p-38 mitogen-activated protein kinase pathway and demonstrates profibrotic changes mediated by matrix metalloproteinase 9, alpha-smooth muscle actin, and fibroblast growth factor 23. Changes in these pathways attenuated acute catecholamine-induced heart failure after propranolol bolus 1 mg/kg. We conclude that propranolol bolus at 1 mg/kg is able to mediate the effects of catecholamine excess through the p-38 mitogen-activated protein kinase pathway, profibrosis, and extrinsic apoptosis pathway., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2024
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