Protective effect of the endothelin antagonist CPU0213 against isoprenaline-induced heart failure by suppressing abnormal expression of leptin, calcineurin and SERCA2a in rats

Abstract

Abstract Heart failure (HF) may be produced by sustained β-adrenoceptor stimulation by causing changes in the expression of endothelin-1 (ET-1), the leptin system, calcineurin and sarcoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) underlying cardiac dysfunction. The aim of this study was to verify whether isoprenaline (ISO)-induced HF is attributed to changes in the above molecular markers, and whether the dual ET-receptor antagonist CPU0213 could reverse the cardiac dysfunction caused by ISO treatment, focusing on these molecular markers. HF was induced in rats by administration of ISO (2 mgkg−1 s.c.) for 10 days. CPU0213 (30 mgkg−1 s.c.) and propranolol (4 mgkg−1 s.c.) were administered on days 7–10. HF developed after 10 days' ISO administration and was manifest as impaired cardiac performance, increased heart weight index, oxidative stress, elevated serum enzymes, and disordered expression of the endothelin system, leptin system, calcineurin and SERCA2a. All these abnormalities were significantly reversed by CPU0213, and the effectiveness of this ET-receptor antagonist was comparable to that of propranolol. Thus, antagonism of ET receptors by CPU0213 normalizes these changes in molecular markers, alleviating HF.