Bosentan Attenuates Compensatory Left Ventricular Hypertrophy Induced by Aortocaval Fistula in Rats

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.