Candesartan ameliorates acute myocardial infarction in rats through inducible nitric oxide synthase, nuclear factor‑κB, monocyte chemoattractant protein‑1, activator protein‑1 and restoration of heat shock protein 72.
Candesartan, an angiotensin II type 1 receptor antagonist, has a variety of biological activities, including antioxidant, anti‑inflammatory and anticancer activities, with specific pharmacological effects. The present study investigated the mechanisms and protective effect of candesartan on acute myocardial infarction in rats. Male Wistar rats (8‑week‑old) were induced as a model of acute myocardial infarction and treated with candesartan (0.25 mg/kg) for 2 weeks. The present study first measured the activities of casein kinase (CK), the MB isoenzyme of creatine kinase (CK‑MB) and lactate dehydrogenase (LDH), the level of cardiac troponin T (cTnT) and infarct size. Subsequently, western blot analysis was performed to analyze the protein expression levels of inducible nitric oxide synthase (iNOS) and heat shock protein 72 (HSP72) in the rats. An enzyme linked immunosorbent assay was used to detect iNOS and nuclear factor‑κB (NF‑κB) activity. In addition, gene expression levels of monocyte chemotactic protein‑1 (MCP‑1) and activating protein‑1 (AP‑1) were determined using reverse transcription‑quantitative polymerase chain reaction analysis. Finally, the activities of caspase‑3 and caspase‑9 were examined using colorimetric assay kits. In the serum of the rat model of acute myocardial infarction, candesartan significantly increased the activities of CK, CK‑MB and LDH, and the level of cTnT. The infarction size was perfected by candesartan treatment. Candesartan significantly reduced the protein expression and activity of iNOS, the activity of NF‑κB p65, and the gene expression levels of MCP‑1 and AP‑1 in the rat model of acute myocardial infarction. Candesartan increased the protein expression of HSP‑72 in the acute myocardial infarction rat model. However, candesartan did not effect the levels of caspase‑3 or caspase‑9 in the rat model of acute myocardial infarction. These results suggested that candesartan ameliorates acute myocardial infarction in rats through iNOS, NF‑κB, MCP‑1 and AP‑1, and the restoration of HSP72.
Department of Cardiovascular Medicine, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Xuefeng
X
Lin
Department of Endocrinology, Shaanxi Provincial People's Hospital, Third Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710068, P.R. China.
Min
M
Wu
First Department of Cardiology, Shaanxi Provincial People's Hospital, Third Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710068, P.R. China.
Bo
B
Liu
First Department of Cardiology, Shaanxi Provincial People's Hospital, Third Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710068, P.R. China.
Junkui
J
Wang
First Department of Cardiology, Shaanxi Provincial People's Hospital, Third Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710068, P.R. China.
Gongchang
G
Guan
Department of Cardiovascular Medicine, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Aiqun
A
Ma
First Department of Cardiology, Shaanxi Provincial People's Hospital, Third Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710068, P.R. China.
Yong
Y
Zhang
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism*; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D050884:HSP72 Heat-Shock Proteins; D016328:NF-kappa B; D013777:Tetrazoles; D018808:Transcription Factor AP-1; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D053148:Caspase 3; D053453:Caspase 9; C081643:candesartan