Amlodipine ameliorates myocardial hypertrophy by inhibiting EGFR phosphorylation.
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.
Liao
Yulin
Y
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0781, Japan.
Asakura
Masanori
M
Takashima
Seiji
S
Kato
Hisakazu
H
Asano
Yoshihiro
Y
Shintani
Yasunori
Y
Minamino
Tetsuo
T
Tomoike
Hitonobu
H
Hori
Masatsugu
M
Kitakaze
Masafumi
M
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
D017311:Amlodipine; D019000:Phosphotyrosine; D004815:Epidermal Growth Factor; D006493:Heparin; D066246:ErbB Receptors; D004837:Epinephrine