Sildenafil prevents the up-regulation of transient receptor potential canonical channels in the development of cardiomyocyte hypertrophy
| Autor: | Kenji Iino, Manabu Murakami, Kyoichi Ono, Kazuhiro Sato, Yutaka Terata, Takayoshi Ohba, Hiroshi Ito, Hiroyuki Watanabe, Hironori Kiso |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Transcriptional Activation
Time Factors Biophysics Cardiomegaly Pharmacology Biochemistry Piperazines Sildenafil Citrate Muscle hypertrophy TRPC6 TRPC1 Rats Sprague-Dawley Transient receptor potential channel Animals Myocytes Cardiac Sulfones Molecular Biology TRPC Cells Cultured TRPC Cation Channels Endothelin-1 NFATC Transcription Factors Chemistry Cell Biology Endothelin 1 PDE5 drug design respiratory tract diseases Rats Up-Regulation Purines cardiovascular system Calcium Endothelin receptor |
| Zdroj: | Biochemical and biophysical research communications. 436(3) |
| ISSN: | 1090-2104 |
| Popis: | 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. Methods and results In cultured neonatal rat cardiomyocytes, a 48 h treatment with 10 nM 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect