title: Angiotensin II receptor blocker irbesartan attenuates cardiac dysfunction induced by myocardial infarction in the presence of renal failure.
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.
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Watanabe
authors.affiliation: Department of Advanced Clinical Science and Therapeutics, The University of Tokyo, Tokyo, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Suzuki
authors.affiliation: Department of Advanced Clinical Science and Therapeutics, The University of Tokyo, Tokyo, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Wakayama
authors.affiliation: Department of Advanced Clinical Science and Therapeutics, The University of Tokyo, Tokyo, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kumagai
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akazawa
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Isobe
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects; D000077405:Irbesartan; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000150:complications* / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D013777:Tetrazoles; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; D000077405:Irbesartan