Comparison of losartan and carvedilol on attenuating inflammatory and oxidative response and preserving energy transcription factors and left ventricular function in dilated cardiomyopathy rats.
We compared the effects of losartan and carvedilol on preserving left ventricular (LV) function in an experimental model of dilated cardiomyopathy (DCM) and examined the mechanisms of their pharmacological effects. The rats were divided into group 1 (normal control), group 2 (DCM), group 3 (DCM plus carvedilol 8 mg/kg/day bid orally), and group 4 (DCM plus losartan 20 mg/kg/day orally). All rats were sacrificed on day 90 following DCM induction. The results indicated that connexin43 protein expression and mRNA expressions of peroxisome proliferator-activated receptor-gamma coactivator-1alpha, endo-thelial nitric oxide synthase, and interleukin-10 were significantly lower, whereas mRNA expressions of endothelin-1 and matrix metalloproteinase-9 were significantly higher in group 2 than in groups 1, 3, and 4 in LV myocardium (all P < 0.05). Additionally, cytochrome C levels in LV myocardium and LV contractility were significantly lower, whereas fibrosis area, cellular apoptosis, and mitochondrial oxidative response of LV myocardium were significantly higher in group 2 than in groups 1, 3, and 4 (all P < 0.005). In conclusion, losartan is comparable to carvedilol in attenuating inflammation, oxidative response, myocardial fibrosis and apoptosis, as well as in preserving energy transcription factors and LV function in DCM.
Chua
Sarah
S
Division of Cardiology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Sheu
Jiunn-Jye
JJ
Chang
Li-Teh
LT
Lee
Fan-Yen
FY
Wu
Chiung-Jen
CJ
Sun
Cheuk-Kwan
CK
Yip
Hon-Kan
HK
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D002227:Carbazoles / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000077261:Carvedilol; D018031:Connexin 43 / Q000378:metabolism; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D011412:Propanolamines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000378:metabolism; D016277:Ventricular Function, Left / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D002227:Carbazoles; D018031:Connexin 43; D011412:Propanolamines; D014157:Transcription Factors; D000077261:Carvedilol; D019808:Losartan