[Reactive oxygen species mediate cultured neonatal rat cardiac myocyte hypertrophy induced by endothelin-1].
The effects of endothelin-1 (ET-1) and other drugs on the reactive oxygen species (ROS) generation and cardiomyocyte hypertrophy were examined in experiments on the cultured neonatal rat cardiomyocytes. The role of ROS on neonatal rat cardiomyocyte hypertrophy induced by ET-1 was studied and the relationship of PKC activation and ROS generation was investigated. The level of intracellular ROS was measured by the ROS-specific probe 2',7'-dichlorofluorescin diacetate (DCF-DA). Cardiomyocyte hypertrophy was determined by the RNA content, the total protein of cells and the cell surface area. The results are as follows. The fluorescence intensity of intracellular DCF-DA increased by 77% in cultured neonatal rat cardiac myocytes treated with ET-1 (10 nmol/L) vs control group. Compared with control group, the fluorescence intensity of intracellular PI, protein content and cell surface area increased by 128%, 87% and 151% respectively (all P<0.01) in cardiac myocytes treated with ET-1 (10 nmol/L). ABT-627, CC, or CAT inhibited the ET-1-induced increase in fluorescence intensity of intracellular DCF-DA by 62%,60% and 51% respectively (all P<0.01), and also attenuated the cardiac hypertrophy. The fluorescence intensity of intracellular DCF-DA increased by 74% (P<0.01) in myocytes treated with PMA (1 micromol/L) vs control group. Therefore, in the course of cardiomyocyte hypertrophy, ET-1 increases intracellular ROS in the cultured neonatal rat cardiac myocytes and inhibits cardiomyocyte hypertrophy induced by ROS. The ET(A) and PKC activation mediate the ROS production and cardiomyocyte hypertrophy induced by ET-1. ROS is necessary in the ET-1-induced cardiomyocyte hypertrophy.
Wang
Yan Zhen
YZ
Department of Pharmacology, Guangzhou Medical College, Guangzhou 510182, China.
Luo
Jian Dong
JD
D000818:Animals; D000831:Animals, Newborn; D049108:Cell Enlargement; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000502:physiology*; D005260:Female; D006984:Hypertrophy; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*
D019332:Endothelin-1; D017382:Reactive Oxygen Species