BACKGROUND: We previously reported that chronic endothelin (ET) receptor blockade ameliorated the survival rate and cardiac hemodynamics in rats with chronic heart failure (CHF) due to myocardial infarction. However, it remains unclear whether ET-1 is involved in the pathophysiology of cardiomyopathy, which is one of the major causes of CHF. Accordingly, we investigated the production of ET-1 in the heart and the effect of chronic ETA receptor blockade on survival rate and cardiac function in the Bio 14.6 hamster, which is an idiopathic model of CHF caused by cardiomyopathy. METHODS AND RESULTS: We used 52-week-old Bio 14.6 cardiomyopathic hamsters and age-matched F1b normal hamsters. The expression of preproET-1 mRNA and the ET-1 level in the hearts were markedly higher in the cardiomyopathic hamsters than in the normal hamsters. The cardiomyopathic hamsters showed severe CHF, illustrated by lower left ventricular (LV) +dP/dt/Pmax and right ventricular (RV) +dP/dt/Pmax and by higher LV end-diastolic pressure (EDP), RVEDP, and central venous pressure compared with the normal hamsters. Long-term (9 weeks) treatment with an ETA antagonist (TA-0201, 1.3 mg. kg-1. d-1) markedly increased survival of cardiomyopathic hamsters (untreated, 16%; TA-0201-treated, 65.2%; P<0.001). After 6 weeks of treatment, LV +dP/dt/Pmax and RV +dP/dt/Pmax were significantly higher and LVEDP and RVEDP were lower in the TA-0201-treated group than in the untreated group, suggesting that chronic TA-0201 treatment effectively prevented deterioration of cardiac dysfunction. CONCLUSIONS: In the cardiomyopathic hamsters with CHF, the production of ET-1 in the heart was markedly increased, and chronic ETA receptor blockade greatly ameliorated survival and cardiac dysfunction. These results suggest that ET-1 plays an important role in the deterioration of CHF caused by cardiomyopathy, and ETA antagonists may exert therapeutic effects in CHF due to cardiomyopathy.
BACKGROUND: We previously reported that chronic endothelin (ET) receptor blockade ameliorated the survival rate and cardiac hemodynamics in rats with chronic heart failure (CHF) due to myocardial infarction. However, it remains unclear whether ET-1 is involved in the pathophysiology of cardiomyopathy, which is one of the major causes of CHF. Accordingly, we investigated the production of ET-1 in the heart and the effect of chronic ETA receptor blockade on survival rate and cardiac function in the Bio 14.6 hamster, which is an idiopathic model of CHF caused by cardiomyopathy. METHODS AND RESULTS: We used 52-week-old Bio 14.6 cardiomyopathic hamsters and age-matched F1b normal hamsters. The expression of preproET-1 mRNA and the ET-1 level in the hearts were markedly higher in the cardiomyopathic hamsters than in the normal hamsters. The cardiomyopathic hamsters showed severe CHF, illustrated by lower left ventricular (LV) +dP/dt/Pmax and right ventricular (RV) +dP/dt/Pmax and by higher LV end-diastolic pressure (EDP), RVEDP, and central venous pressure compared with the normal hamsters. Long-term (9 weeks) treatment with an ETA antagonist (TA-0201, 1.3 mg. kg-1. d-1) markedly increased survival of cardiomyopathic hamsters (untreated, 16%; TA-0201-treated, 65.2%; P<0.001). After 6 weeks of treatment, LV +dP/dt/Pmax and RV +dP/dt/Pmax were significantly higher and LVEDP and RVEDP were lower in the TA-0201-treated group than in the untreated group, suggesting that chronic TA-0201 treatment effectively prevented deterioration of cardiac dysfunction. CONCLUSIONS: In the cardiomyopathic hamsters with CHF, the production of ET-1 in the heart was markedly increased, and chronic ETA receptor blockade greatly ameliorated survival and cardiac dysfunction. These results suggest that ET-1 plays an important role in the deterioration of CHF caused by cardiomyopathy, and ETA antagonists may exert therapeutic effects in CHF due to cardiomyopathy.
Authors: Roger Dillier; Richard Kobza; Susanne Erne; Michel Zuber; Patricia Arand; Paul Erne Journal: Cardiol Res Pract Date: 2010-10-17 Impact factor: 1.866
Authors: Lorenz H Lehmann; Julia S Rostosky; Sebastian J Buss; Michael M Kreusser; Jutta Krebs; Walter Mier; Frank Enseleit; Katharina Spiger; Stefan E Hardt; Thomas Wieland; Markus Haass; Thomas F Lüscher; Michael D Schneider; Rosanna Parlato; Hermann-Josef Gröne; Uwe Haberkorn; Masashi Yanagisawa; Hugo A Katus; Johannes Backs Journal: Proc Natl Acad Sci U S A Date: 2014-09-02 Impact factor: 11.205