The Protective Effects of Compound 21 and Valsartan in Isoproterenol-Induced Myocardial Injury in Rats.

Abstract

This study investigated the protective effects of Compound 21 (C21), the first specific non-peptide AT2 receptor agonist, on cardiac injury in rats with isoproterenol-induced heart failure in vivo and compared it with valsartan, an AT1 receptor antagonist. In this study, 56 Wistar albino male rats (estimated body weights 250-400 g) were divided into eight groups (n = 7). Group 1 (Control) received no drug. Group 2 (ISO) was given 180 mg/kg of isoproterenol subcutaneously (s.c.); two doses were administered at 24-h intervals on days 29 and 30 of the experiment. Groups 3, 4, and 5 were given valsartan (30 mg/kg orally), C21 (0.03 mg/kg intraperitoneally), and a combination of Valsartan + C21, respectively, for 30 days. Groups 6, 7, and 8 were administered Valsartan, C21, and Valsartan + C21 in the same application, duration, and dose, respectively, and isoproterenol (180 mg/kg s.c.) was given on days 29 and 30 of the experiment. Transthoracic echocardiography was performed on the rats at the beginning and end of the experiment. Blood pressure, heart rate, and ECG alterations were monitored via a carotid artery cannula at the end of the experiment. Histopathological and biochemical measurements were performed on the cardiac tissue of the rats. For histopathological findings, C21 and Valsartan + C21 combination therapy significantly reduced the development of heart failure compared to valsartan alone. Also, the protective effect of C21 on myocardial injury was superior to that of valsartan. According to the results of echocardiographic and biochemical evaluations, C21, and Valsartan showed protective effects against heart failure. C21, valsartan, and combined therapy significantly prevented the decrease of ejection fraction. This report describes the cardioprotective effects of C21 and valsartan in ISO-induced myocardial damage.

• Authors: Zeynep Ulutas, Necip Ermis, Onural Ozhan, Hakan Parlakpinar, Nigar Vardi, Burhan Ates, Cemil Colak
• Journal: Cardiovascular toxicology (Cardiovasc Toxicol) Vol. 21 Issue 1 Pg. 17-28 (01 2021) ISSN: 1559-0259 [Electronic] United States
• PMID: 32648158 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Agtr2 protein, rat
• Angiotensin II Type 1 Receptor Blockers
• N-butyloxycarbonyl-3-(4-imidazol-1-ylmethylphenyl)-5-isobutylthiophene-2-sulfonamide
• Receptor, Angiotensin, Type 2
• Sulfonamides
• Thiophenes
• Valsartan
• Isoproterenol

Topics

• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Animals
• Disease Models, Animal
• Drug Therapy, Combination
• Heart Failure (chemically induced, pathology, physiopathology, prevention & control)
• Heart Rate (drug effects)
• Isoproterenol
• Male
• Myocardium (pathology)
• Rats, Wistar
• Receptor, Angiotensin, Type 2 (agonists)
• Stroke Volume (drug effects)
• Sulfonamides (pharmacology)
• Thiophenes (pharmacology)
• Valsartan (pharmacology)
• Ventricular Function, Left (drug effects)
• Rats