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Biochem Biophys Res Commun. 2013 Jul 5;436(3):514-8. doi: 10.1016/j.bbrc.2013.06.002. Epub 2013 Jun 10.

Sildenafil prevents the up-regulation of transient receptor potential canonical channels in the development of cardiomyocyte hypertrophy.

Author information

1
Department of Internal Medicine, Division of Cardiovascular and Respiratory Medicine, Akita University Graduate School of Medicine, Japan.

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.

METHODS AND 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.

KEYWORDS:

Ca(2+) entry; Cardiomyocyte hypertrophy; Sildenafil; TRPC channels

PMID:
23764398
DOI:
10.1016/j.bbrc.2013.06.002
[Indexed for MEDLINE]

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