Open AccessPitavastatin Inhibits Cardiac Hypertrophy in a Rat Model of Progressive Renal Injury
Author(s) -
Hitomi Takahashi,
Yasuchika Takeishi,
Takanori Arimoto,
Tetsuro Shishido,
Tsuneo Konta,
Yo Koyama,
Takeshi Niizeki,
Isao Kubota
Publication year - 2005
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/01.fjc.0000177984.76186.70
Subject(s) - pitavastatin , medicine , angiotensin ii , endocrinology , mapk/erk pathway , muscle hypertrophy , renin–angiotensin system , heart failure , statin , blood pressure , kinase , chemistry , biochemistry
Increased cardiovascular mortality is an unresolved problem of chronic renal failure. Cardiac hypertrophy, observed in many patients with chronic renal failure, is a major risk factor for cardiovascular death. The purpose of the present study was to examine the effects of pitavastatin on cardiac hypertrophy in a progressive renal injury rat model by subtotal nephrectomy (SNx). Because we previously reported that angiotensin II played a pivotal role in cardiac hypertrophy of SNx rats, we first investigated the effects of pitavastatin on angiotensin II-induced activation of extracellular signal-regulated kinase (ERK) and serum response element (SRE) DNA-binding activity using neonatal rat cardiomyocytes. Angiotensin II-induced ERK activation was attenuated by pretreatment with pitavastatin. Luciferase assay revealed that angiotensin II-induced increase in SRE DNA-binding activity was inhibited by pitavastatin. We next examined the effect of pitavastatin on cardiac hypertrophy of SNx rats in vivo. Treatment with pitavastatin prevented ERK activation and cardiac hypertrophy in SNx rats without changes in blood pressure. The increased expression of atrial natriuretic factor mRNA in SNx rat hearts was significantly attenuated by the treatment with pitavastatin. These results suggest that pitavastatin has a beneficial effect on cardiac hypertrophy in renal failure through preventing the activation of ERK.