Comparison of losartan and carvedilol on attenuating inflammatory and oxidative response and preserving energy transcription factors and left ventricular function in dilated cardiomyopathy rats

Sarah Chua, Jiunn Jye Sheu, Li Teh Chang, Fan Yen Lee, Chiung Jen Wu, Cheuk Kwan Sun, Hon Kan Yip

Research output: Contribution to journalJournal Article peer-review

14 Scopus citations

Abstract

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-γ coactivator-1α, endothelial 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.

Original languageEnglish
Pages (from-to)605-619
Number of pages15
JournalInternational Heart Journal
Volume49
Issue number5
DOIs
StatePublished - 2008
Externally publishedYes

Keywords

  • Dilated cardiomyopathy
  • Inflammation
  • Pharmacological modulation

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