Involvement of endothelin-1 in hypoxia-induced cardiomyocyte apoptosis.
- Author:
Hong LU
1
;
Li LIN
;
Xiong-Hong YAN
;
Yuan WANG
;
An-Jing REN
;
Wen-Jun YUAN
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Animals, Newborn; Apoptosis; Cell Hypoxia; Cells, Cultured; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Endothelin-1; physiology; Myocytes, Cardiac; metabolism; pathology; Rats; Rats, Sprague-Dawley
- From: Chinese Journal of Applied Physiology 2006;22(2):147-151
- CountryChina
- Language:Chinese
-
Abstract:
AIMTo investigate the effect of endogenous endothelin-1 (ET-1) on cardiomyocyte apoptosis induced by hypoxia and its possible mechanism.
METHODSCultured neonatal rat cardiomyocytes were divided into control group and ET receptor antagonist group. Control group was given DMEM only and ET receptor antagonist group was treated with ET receptor subtype A (ET(A)) receptor antagonist BQ610 and BQ123 or ET(B) receptor antagonist BQ788 and subjected to hypoxia for 24 h. The presence of apoptosis in cardiomyocytes was evaluated by TUNEL analysis and flow cytometry (FCM).
RESULTSTUNEL analysis showed that the percentage of positive apoptotic cells in BQ610 5 micromol/L group was 13.2% +/- 3.7%, significantly lower than that in hypoxia group (24.2% +/- 2.2%, P < 0.01). FCM showed that BQ123 (0.04, 0.2 and 1.0 micromol/L) inhibited hypoxia-induced cardiomyocyte apoptosis and increased cardiomyocyte survival rate in a dose-dependent manner, while BQ788 did not show such effects.
CONCLUSIONThese findings suggest that endogenous ET-1 aggravates hypoxia-induced cardiomyocyte apoptosis and this effect is mediated through ET(A) receptor-dependent pathways.
