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Protein kinase C and extracellular signal regulated kinase are involved in cardiac hypertrophy of rats with progressive renal injury
Author(s) -
Takahashi H.,
Takeishi Y.,
Miyamoto T.,
Shishido T.,
Arimoto T.,
Konta T.,
Miyashita T.,
Ito M.,
Kubota I.
Publication year - 2004
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2004.01304.x
Subject(s) - medicine , endocrinology , protein kinase c , angiotensin ii , muscle hypertrophy , kinase , signal transduction , mapk/erk pathway , biology , receptor , microbiology and biotechnology
Increased cardiovascular mortality is an unresolved problem in patients with chronic renal failure. Cardiac hypertrophy is observed in the majority of patients with chronic renal failure undergoing haemodialysis. However, the mechanisms, including signal transduction pathways, responsible for cardiac hypertrophy in renal failure remain unknown. We examined the subcellular localization of protein kinase C (PKC) isoforms and phosphorylation activities of 3 mitogen‐activated protein (MAP) kinase families in hypertrophied hearts of progressive renal injury rat model by subtotal nephrectomy (SNx). We also examined the effects of a novel angiotensin II type‐1 receptor antagonist, CS‐866, on the PKC translocation, MAP kinase activity and cardiac hypertrophy in SNx rats. The left ventricle/body weight ratios were significantly larger in SNx rats than in sham rats at 1, 2, and 4 weeks after surgery. The translocation of PKCα and ɛ isoforms to membranous fraction was observed in SNx rat hearts at 1, 2, and 4 weeks after surgery. Activation of extracellular signal regulated kinase (ERK) 1/2, but not p38 MAP kinase and c‐Jun N‐terminal kinase (JNK), was observed at 1 and 2 weeks after surgery. Angiotensin II receptor blockade with CS‐866 (1 mg kg −1 day −1 ) prevented cardiac hypertrophy, PKC translocation and ERK1/2 activation in SNx rats without significant changes in blood pressure. These data suggest that PKC and ERK1/2 are activated by an angiotensin II receptor‐mediated pathway and might play an important role in the progression of cardiac hypertrophy in renal failure.