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Mechanical stretch induces endothelial nitric oxide synthase gene expression in neonatal rat cardiomyocytes.

Abstract：

:1. Mechanical stretch leads to cardiac hypertrophy and may ultimately cause heart failure. However, the effect of mechanical stretch on gene induction in cardiomyocytes remains to be determined. 2. In the present study, we compared transcript profiles of mechanically stretched neonatal rat cardiomyocytes with those of unstretched cells using cDNA microarrays. The microarrays contained probes for 480 known genes, including those involved in signal transduction, cell cycle regulation, the cytoskeleton and cell motility. Eighteen genes, including the eNOS gene, were identified as having significantly differential expression in response to mechanical stretch in cardiomyocytes. 3. Northern and western blot analysis further quantified the expression of the eNOS gene. Mechanical stretch increased constitutive NOS activity and nitric oxide (NO) production. The NO donor s-nitroso-N-acetylpenicillamine (SNAP) inhibited mechanical stretch-stimulated protein synthesis, as measured by [3H]-leucine uptake. In addition, cardiomyocytes were infected with adenoviral vectors encoding cDNA for eNOS (Ad-eNOS) and a phosphoglycerate kinase (PGK) empty vector (Ad-PGK). In contrast with Ad-PGK-infected cells, in cardiomyocytes infected with Ad-eNOS, there was increased calcium-dependent NOS activity and nitrite production. Cardiomyocytes infected with Ad-eNOS exhibited diminished mechanical stretch-stimulated protein synthesis. In contrast, in eNOS-knockdown cells, the increased eNOS protein levels and NOS activity induced by mechanical stretch were abolished, but protein synthesis was enhanced. 4. The results of the present study indicate that eNOS gene expression is induced by mechanical stretch, leading to increased constitutive NOS activity and NO production, which may be a negative regulator in cardiomyocyte hypertrophy.

journal_name

Clin Exp Pharmacol Physiol

journal_title

Clinical and experimental pharmacology & physiology

authors

Cheng TH,Chen JJ,Shih NL,Lin JW,Liu JC,Chen YL,Chen CH,Chen JJ

doi

10.1111/j.1440-1681.2008.05100.x

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

559-66

issue

5-6

eissn

0305-1870

issn

1440-1681

pii

CEP5100

journal_volume

pub_type

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Mechanical stretch induces endothelial nitric oxide synthase gene expression in neonatal rat cardiomyocytes.