Angiotensin II receptor blocker irbesartan attenuates cardiac dysfunction induced by myocardial infarction in the presence of renal failure

Ryo Watanabe, Jun Ichi Suzuki, Kouji Wakayama, Hidetoshi Kumagai, Yuichi Ikeda, Hiroshi Akazawa, Issei Komuro, Mitsuaki Isobe

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The activity of the renin-angiotensin system is known to be a key factor in the pathophysiology of heart failure and renal failure. Irbesartan, an angiotensin II receptor blocker, has non-hemodynamic cardiovascular and renal protective effects. However, the effect of irbesartan on heart failure complicated by renal failure has not yet been elucidated. Thus the purpose of this study was to evaluate the effect of irbesartan on the pathophysiology of cardiorenal syndrome in a rat model. Subtotal nephrectomy (NTX) was performed in rats was using a two-step surgical procedure. Twenty-eight days after NTX, myocardial infarction (MI) was induced by ligation of the left anterior descending coronary artery. The animals were orally administered vehicle or irbesartan (10 mg kg -1 day -1) after NTX. The hearts were harvested 28 days after MI. MI with NTX model rats showed an impaired post-MI survival rate and enhanced cardiac inflammation in comparison to MI without NTX rats. Although irbesartan treatment did not improve the survival rate, it suppressed cardiac inflammation, left ventricular function decline, cardiac fibrosis, hypertrophy of cardiomyocytes and renal fibrosis in MI with NTX rats. Moreover, increases in protein expression levels related to oxidative stress and inflammation (NADPH oxidase 4, phospho-nuclear factor-κB and phospho-c-Jun) observed in the hearts of non-treated MI with NTX rats were attenuated by irbesartan treatment. These effects of irbesartan treatment were independent of blood pressure. We conclude that irbesartan has a cardioprotective effect after MI when renal dysfunction is present.

Original languageEnglish (US)
Pages (from-to)237-244
Number of pages8
JournalHypertension Research
Volume39
Issue number4
DOIs
StatePublished - Apr 1 2016

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Keywords

  • angiotensin II receptor blocker
  • cardioprotective effect
  • cardiorenal syndrome

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Watanabe, R., Suzuki, J. I., Wakayama, K., Kumagai, H., Ikeda, Y., Akazawa, H., Komuro, I., & Isobe, M. (2016). Angiotensin II receptor blocker irbesartan attenuates cardiac dysfunction induced by myocardial infarction in the presence of renal failure. Hypertension Research, 39(4), 237-244. https://doi.org/10.1038/hr.2015.141