Pretreatment with catalpol attenuates cardiac dysfunction following myocardial infarction through regulating apelin/APJ signaling pathway and inhibiting cardiomyocyte apoptosis in rats

OBJECTIVE: To investigate the effects and mechanisms of catalpol on cardiac function in rats with isoproterenol (ISO)-induced myocardial infarction (MI). METHODS: Adult male Wistar rats were divided into four groups: control group, ISO group, catalpol (L, low dose) group, and catalpol (H, high dose) group. Isoproterenol (85 mg/kg) was injected subcutaneously for 2 consecutive days to induce experimental MI. At the end of experiment, the effects of catalpol on cardiac function; apelin levels; apoptosis index; apelin, APJ, Bcl-2, and Bax protein expression; and caspase-3/9 activities were investigated. RESULTS: The rats in the ISO group showed lower left ventricular maximum rate of positive or negative pressure development (±LVdp/dtmax) and left ventricular end-systolic pressure (LVSP) and higher left ventricular end-diastolic pressure (LVEDP) than those in the control group, suggesting severe cardiac dysfunction. Interestingly, catalpol administration significantly ameliorated the ISO-induced cardiac dysfunction. The groups administered low and high dosages catalpol (5 and 10 mg/kg/day, respectively) showed higher ±LVdp/dtmax and LVSP and lower LVEDP than the group administered ISO alone. Catalpol markedly upregulated apelin levels in the plasma and myocardium. Further, catalpol increased the apelin and APJ expression levels in the myocardium of the ISO-treated rats. In addition, catalpol pretreatment inhibited cardiomyocyte apoptosis as indicated by a decrease in the TUNEL-positive cell percentage, alterations in the Bax and Bcl-2 expression levels, and a decline in caspase-3 and caspase-9 activities. CONCLUSION: Our results revealed that catalpol can improve cardiac function. Its protective effects may be linked to the enhancement of myocardium contractility, regulation of the apelin/APJ pathway, and inhibition of cardiomyocyte apoptosis.