J Cardiovasc Pharmacol. 2024 Apr 10. doi: 10.1097/FJC.0000000000001571. Online ahead of print.
ABSTRACT
Hyper-catecholaminergic 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 hyper-acute 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 (LV, p= 0.021; RV, p=0.021), with upregulation of reactive oxidative species and other pro-fibrosis proteins, after catecholamine infusion alone. After one propranolol 1 mg/kg bolus, the levels of phosphorylated-p38 returned to levels comparable to sham (LV, p= 0.021; RV, p= 0.043), with additional findings including downregulation of the apoptotic pathway and pro-fibrotic proteins. We conclude that catecholamine-induced heart failure exerts damage through the p-38 MAP kinase pathway, and demonstrates pro-fibrotic 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 MAP kinase pathway, pro-fibrosis, and extrinsic apoptosis pathway.
PMID:38922579 | DOI:10.1097/FJC.0000000000001571
