The β 2 -adrenergic receptor agonist formoterol attenuates necrosis and apoptosis in the rat myocardium under experimental stress-induced cardiac injury.

Autor: Naryzhnaya NV; Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia, 111a, Kievskaya str., Tomsk, 634012, Russian Federation., Logvinov SV; Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia, 111a, Kievskaya str., Tomsk, 634012, Russian Federation.; Siberian State Medical University, 2, Moskovsky tract, Tomsk, 634050, Russian Federation., Kurbatov BK; Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia, 111a, Kievskaya str., Tomsk, 634012, Russian Federation., Derkachev IA; Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia, 111a, Kievskaya str., Tomsk, 634012, Russian Federation., Mustafina LR; Siberian State Medical University, 2, Moskovsky tract, Tomsk, 634050, Russian Federation., Gorbunov AS; Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia, 111a, Kievskaya str., Tomsk, 634012, Russian Federation., Sirotina MA; Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia, 111a, Kievskaya str., Tomsk, 634012, Russian Federation., Kilin M; Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia, 111a, Kievskaya str., Tomsk, 634012, Russian Federation., Gusakova SV; Siberian State Medical University, 2, Moskovsky tract, Tomsk, 634050, Russian Federation., Maslov LN; Cardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia, 111a, Kievskaya str., Tomsk, 634012, Russian Federation.
Jazyk: angličtina
Zdroj: Fundamental & clinical pharmacology [Fundam Clin Pharmacol] 2024 Jul 02. Date of Electronic Publication: 2024 Jul 02.
DOI: 10.1111/fcp.13026
Abstrakt: Background: Currently, there is no effective therapy for takotsubo syndrome (stress-induced cardiac injury in humans) in the clinics. It has previously been shown that β 2 -adrenergic receptor (β 2 -AR) agonist formoterol reduces cardiomyocyte injury in experimental takotsubo syndrome.
Objectives: The aim of this study was to investigate whether formoterol prevents apoptosis and necrosis of cardiomyocytes and endothelial cells in stress-induced cardiomyopathy.
Methods: Stress-induced cardiac injury was induced by immobilization of rats for 2, 6, and 24 hours.
Results: The myocardium of stressed rats showed a reduction in contractility and histological manifestations of cardiomyocyte damage: karyopyknosis, perinuclear edema of cardiomyocytes and endothelial cells, and microcirculation disturbances augmented with extended exposure to stress. In addition, apoptosis of endothelial cells was detected 6 hours after the onset of stress and peaked at 24 hours. Apoptosis of cardiomyocytes significantly gained only after 24 hours of stress exposure. These morphological alterations were associated with increased levels of serum creatine kinase-MB, syndecan-1, and thrombomodulin after 24 hours of stress. Administration of β 2 -AR agonist formoterol (50 μg/kg) four times during 24-hour stress exposure led to the improvement in myocardial inotropy, decrease in the severity of histological signatures, reduction in the number of TUNEL-positive cardiomyocytes, serum creatine kinase-MB, syndecan-1, and thrombomodulin levels.
Conclusion: Present data suggest that apoptosis and necrosis of cardiomyocytes and necrosis of endothelial cells in stress-induced cardiac injury can be mitigated by activation of the β 2 -AR. However, formoterol did not eliminate completely cardiomyocyte apoptosis, histological alterations, or endothelium injury markers under stress.
(© 2024 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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