Propranolol Alleviates Cardiac Injury After Acute Catecholamine Infusion Through p38-MAPK Pathways.
J Cardiovasc Pharmacol
; 84(1): 110-117, 2024 Jul 01.
Article
in En
| MEDLINE
| ID: mdl-38922579
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Propranolol
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Fibrosis
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Norepinephrine
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Rats, Sprague-Dawley
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Adrenergic beta-Antagonists
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P38 Mitogen-Activated Protein Kinases
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Heart Failure
Limits:
Animals
Language:
En
Journal:
J Cardiovasc Pharmacol
Year:
2024
Document type:
Article
Affiliation country:
Taiwán