[Involvement of endothelin-1 in hypoxia-induced cardiomyocyte apoptosis].

Abstract

AIM:

To investigate the effect of endogenous endothelin-1 (ET-1) on cardiomyocyte apoptosis induced by hypoxia and its possible mechanism.

METHODS:

Cultured 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).

RESULTS:

TUNEL 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.

CONCLUSION:

These findings suggest that endogenous ET-1 aggravates hypoxia-induced cardiomyocyte apoptosis and this effect is mediated through ET(A) receptor-dependent pathways.

• Authors: Hong Lu, Li Lin, Xiong-Hong Yan, Yuan Wang, An-Jing Ren, Wen-Jun Yuan
• Journal: Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology (Zhongguo Ying Yong Sheng Li Xue Za Zhi) Vol. 22 Issue 2 Pg. 147-51 (May 2006) ISSN: 1000-6834 [Print] China
• PMID: 21162225 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endothelin A Receptor Antagonists
• Endothelin B Receptor Antagonists
• Endothelin-1

Topics

• 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