title: Protein kinase C and extracellular signal regulated kinase are involved in cardiac hypertrophy of rats with progressive renal injury.
abstract: 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 PKCalpha and epsilon 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.
authors.affiliation: Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Takeishi
authors.forename: T
authors.initials: T
authors.lastname: Miyamoto
authors.forename: T
authors.initials: T
authors.lastname: Shishido
authors.forename: T
authors.initials: T
authors.lastname: Arimoto
authors.forename: T
authors.initials: T
authors.lastname: Konta
authors.forename: T
authors.initials: T
authors.lastname: Miyashita
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: I
authors.initials: I
authors.lastname: Kubota
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D006352:Heart Ventricles / Q000473:pathology; D007093:Imidazoles / Q000494:pharmacology; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D000068557:Olmesartan Medoxomil; D009929:Organ Size; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology; D015398:Signal Transduction; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000068557:Olmesartan Medoxomil; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases