All issues > Volume 46(7); 2003

Original Article

J Korean Pediatr Soc. 2003;46(7):668-678. Published online July 15, 2003.

Effects of Endothelin A Receptor Antagonist to Cellular Proliferation and Apoptosis in Neonatal Rat Heart

Byung Min BM Choi¹, Kee Hwan KH Yoo¹, Young Sook YS Hong¹, Joo Won JW Lee¹, Soon Kyum SK Kim¹

¹Department of Pediatrics, College of Medicine, Korea University, Seoul, Korea

Correspondence Joo Won JW Lee ,Email: guroped@korea.ac.kr

Abstract

Purpose
: In order to investigate the role of endothelins in the cardiac development, the present study was designed to examine the effects of endothelin A receptor(ETAR) antagonist to the cellular proliferation and apoptosis in the neonatal rat heart. In addition, the expression of various regulatory genes in protein and mRNA levels by ETAR antagonist were examined.
Methods
: Neonatal Spargue-Dawley rats were separated into two groups. The BMS group(N=22) was treated with the selective ETAR antagonist(Bristo-Myers Squibb-182874; 300 mg/Kg/day) and the control group(N=20) with normal saline for seven days by orogastric tube. On the following day, their hearts were harvested for determination of apoptosis by modified TUNEL technique and cellular proliferation by PCNA stain. In addition to this, Western blottings and RT-PCRs of bcl-x, clusterin, p53 and TGF-β1 were performed.
Results
: The BMS group resulted in a reduced body weight, but not a significantly reduced heart weight. In the BMS group, cardiac apoptotic cells and PCNA positive cells were decreased(P<0.05). In the BMS group, clusterin and bcl-x protein expressions were increased(P<0.05), but p53 and TGF-β1 protein expressions remained the same. In the BMS group, clusterin and TGF-β1 mRNA expressions were increased(P<0.05), but bcl-x and p53 mRNA expressions remained the same.
Conclusion
: ETAR antagonist treatment decreases cell turnover in the developing rat heart, which may account for the role of endothelins on modulating cardiac growth. These changes may be affected by clusterin and bcl-x expressions. These results support that there are some roles of endothelin and ETAR in the cellular level of early neonatal cardiac growth.

Keywords :Endothelin A receptor antagonist, Bristo-Myers Squibb-182874, Cellular proliferation, Apoptosis, Bcl-x, Clusterin, p53, TGF-β1, Developing heart, Rat