title: Amlodipine ameliorates myocardial hypertrophy by inhibiting EGFR phosphorylation.
abstract: The effects of long-acting calcium channel blockers on pressure overload-induced cardiac hypertrophy have been little studied in experimental animals and the underlying mechanisms are not fully understood. We previously reported that cardiomyocyte hypertrophy could be induced via phosphorylation of the epidermal growth factor receptor (EGFR). In this study, we investigated whether amlodipine attenuates cardiac hypertrophy by inhibiting EGFR phosphorylation. We found that amlodipine dose-dependently inhibited epinephrine-induced protein synthesis and EGFR phosphorylation in cultured neonatal rat cardiomyocytes. Our in vivo study revealed that amlodipine could ameliorate myocardial hypertrophy induced by transverse aortic constriction (TAC) in C57/B6 mice. One week after TAC, amlodipine treatment (3 mg/kg/day) significantly reduced the heart-to-body weight ratio (6.04 +/- 0.16 mg/g vs. 6.90 +/- 0.45 mg/g in untreated TAC mice, P < 0.01). These results indicate that amlodipine ameliorates cardiomyocyte hypertrophy via inhibition of EGFR phosphorylation.
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0781, Japan.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Liao
authors.forename: Masanori
authors.initials: M
authors.lastname: Asakura
authors.forename: Seiji
authors.initials: S
authors.lastname: Takashima
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Kato
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Asano
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Shintani
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Minamino
authors.forename: Hitonobu
authors.initials: H
authors.lastname: Tomoike
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
mesh_terms: D017311:Amlodipine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats
chemical_list: D017311:Amlodipine; D019000:Phosphotyrosine; D004815:Epidermal Growth Factor; D006493:Heparin; D066246:ErbB Receptors; D004837:Epinephrine