Bosentan Attenuates Compensatory Left Ventricular Hypertrophy Induced by Aortocaval Fistula in Rats.
10.4070/kcj.2005.35.9.665
- Author:
Dong Seok LEE
1
;
Doo Kwun KIM
;
Sung Min CHOI
;
Young Kyu KIM
;
Bok Hyun KO
;
Yong Wook JUNG
Author Information
1. Department of Pediatrics, College of Medicine, Dongguk University, Gyeongju, Korea. lds117@dongguk.ac.kr
- Publication Type:Original Article
- Keywords:
Endothelin;
Pulmonary circulation;
Hypertrophy;
Hypertension, pulmonary
- MeSH:
Animals;
Arterioles;
Cardiomegaly;
Endothelin-1;
Endothelins;
Fistula*;
Heart;
Heart Failure;
Hypertension, Pulmonary;
Hypertrophy;
Hypertrophy, Left Ventricular*;
Lung;
Plasma;
Pulmonary Artery;
Pulmonary Circulation;
Rats*;
Receptors, Endothelin
- From:Korean Circulation Journal
2005;35(9):665-671
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND AND OBJECTIVES: Endothelin-1 (ET-1) is increased in advanced congestive heart failure and pulmonary hypertension associated with increased pulmonary blood flow. The role of ET-1 and the protective effect of the dual endothelin receptor antagonist, Bosentan, were investigated in overcirculation-induced compensatory left ventricular (LV) hypertrophy using aortocaval fistula (AVF) rats. MATERIALS AND METHODS: Twenty one 8-week-old rats were randomized into sham control, AVF and Bosentan (100 mg/kg/day) treatment groups. Four weeks later, the cardiac hypertrophy, pulmonary artery morphometry, plasma and tissue levels of ET-1 and the immunoreactive signal of ET-1 were evaluated in the heart and lung tissues. RESULTS: Chronic AVF developed LV hypertrophy and markedly increased the plasma and tissue ET-1 levels in the heart and lung compared to those in the controls (p<0.05), and these changes were attenuated by Bosentan treatment (p<0.05). However, the wall thickness of the pulmonary arteriole did not change. In addition, the immunoreactive signal of ET-1 was increased in the heart after AVF compared with the controls, and was also slightly decreased with Bosentan treatment. However, there were no remarkable differences in the lung tissue. CONCLUSION: ET-1 was up-regulated in compensatory LV hypertrophy induced by AVF. Bosentan attenuates cardiac hypertrophy and decreases the ET-1 levels in the plasma, heart and lung. Therefore, it is speculate that chronic treatment of an ET-1 antagonist may provide an additional strategy for AVF-induced compensatory LV hypertrophy.
