title: Sildenafil prevents the up-regulation of transient receptor potential canonical channels in the development of cardiomyocyte hypertrophy.
abstract: BACKGROUND
  Transient receptor potential canonical (TRPCs) channels are up-regulated in the development of cardiac hypertrophy. Sildenafil inhibits TRPC6 activation and expression, leading to the prevention of cardiac hypertrophy. However, the effects of sildenafil on the expression of other TRPCs remain unknown. We hypothesized that in addition to its effects of TRPC6, sildenafil blocks the up-regulation of other TRPC channels to suppress cardiomyocyte hypertrophy.
  
  
  RESULTS
  In cultured neonatal rat cardiomyocytes, a 48 h treatment with 10nM endothelin (ET)-1 induced hypertrophic responses characterized by nuclear factor of activated T cells activation and enhancement of brain natriuretic peptide expression and cell surface area. Co-treatment with sildenafil (1 μM, 48 h) inhibited these ET-1-induced hypertrophic responses. Although ET-1 enhanced the gene expression of TRPCs, sildenafil inhibited the enhanced gene expression of TRPC1, C3 and C6. Moreover, co-treatment with sildenafil abolished the augmentation of SOCE in the hypertrophied cardiomyocytes.
  
  
  CONCLUSIONS
  These results suggest that sildenafil inhibits cardiomyocyte hypertrophy by suppressing the up-regulation of TRPC expression.
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Akita University Graduate School of Medicine, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Kiso
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ohba
authors.forename: Kenji
authors.initials: K
authors.lastname: Iino
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sato
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Terata
authors.forename: Manabu
authors.initials: M
authors.lastname: Murakami
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Ono
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Watanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000473:pathology*; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology*; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D019332:Endothelin-1; D050778:NFATC Transcription Factors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; C096351:transient receptor potential cation channel, subfamily C, member 1; D000068677:Sildenafil Citrate; D002118:Calcium
keywords: Ca(2+) entry; Cardiomyocyte hypertrophy; Sildenafil; TRPC channels