Mechanism of endothelin receptor antagonist CPU0213 and calcium antagonist CPU86017 ameliorated rats′ heart failure induced by isoproterenol

The purpose of this experiment was to verify whether endothelin receptor antagonist CPU0213 and calcium antagonist CPU86017 improved isoproterenol (ISO)-induced heart failure in rats by inhibiting p66Shc and PKCε .40 SD male rats were randomly divided into 5 groups.Except for the normal group,the other groups were given isoproterenol for 10 d (1mg/kg,sc).Three treatment groups (sc,mg/kg,from day 10-11) included: aminoguanidine group 30 and CPU0213 group 30 and CPU86017 group 4.It was found that mRNA or the protein expressions of endothelin receptor A (ET_A),iNOS,p66Shc,PKCε,OBRb,NADPH oxidase p67 ^phox and leptin increased in ISO group.After drug treatment ,the above abnormal indicators were mitigated and even reversed.Hence,it suggested that CPU0213 and CPU86017 improved the ISO- induced heart failure by inhibiting the endothelin receptor and oxidative stress and down-regulating the expressions of p66Shc and PKCε.