sm-346 and Heart-Failure

Original translational rat model of chronic heart failure provoked by experimental anterior transmural myocardium infarction was employed to examine the preventive action of anxiolytic Afobazole (15 mg/kg/day administered intraperitoneally during the first 15 days after coronary occlusion) on the development of the heart failure assessed in 3 months after infarction. Afobazole prevented the development of pathologic remodeling of the myocardium, maintained its inotropic function, and decreased the plasma level of brain natriuretic peptide known as a biochemical marker of chronic heart failure. In the myocardium, Afobazole down-regulated overexpression of the genes induced in chronic heart failure and assessed by corresponding RNA levels, which code angiotensin (AT1A-R), vasopressin (V1A-R), and glucocorticoid (GR) receptors as well as Epac2 protein. The revealed biochemical changes are consistent with the data on cardioprotective action of Afobazole.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Animals, Outbred Strains; Anti-Anxiety Agents; Benzimidazoles; Biomarkers; Cardiotonic Agents; Coronary Occlusion; Coronary Vessels; Drug Administration Schedule; Drug Repositioning; Gene Expression Regulation; Guanine Nucleotide Exchange Factors; Heart Failure; Male; Morpholines; Myocardial Infarction; Myocardium; Natriuretic Peptide, Brain; Rats; Receptor, Angiotensin, Type 1; Receptors, Glucocorticoid; Receptors, Vasopressin

Delayed cardioprotective effects of anxiolytic Afobazole (15 mg/kg, intraperitoneally for 14 days) were evaluated using dynamic echocardiographic recordings on days 2, 15, 56, and 98 after experimental myocardial infarction modeling (rat model of acute myocardial ischemia). The cardiotropic activity of Afobazole is assumed to be related to its agonistic effects on σ

Topics: Animals; Benzimidazoles; Echocardiography; Heart Failure; Male; Morpholines; Myocardial Infarction; Rats; Stroke Volume; Ventricular Function, Left