Treatment with oestrogen‐receptor agonists or oxytocin in conjunction with exercise protects against myocardial infarction in ovariectomized rats

New Findings What is the central question of this study? Could the activation of oxytocin or oestrogen receptors be protective against myocardial injury after ovariectomy? If so, would exercising have an additional ameliorating effect? What is the main finding and its importance? The results revealed that when accompanied by exercise, both oestrogen receptor agonists and oxytocin improved cardiac dysfunction, inhibited the generation of pro‐inflammatory cytokines and reduced myocardial injury in ovariectomized female rats, suggesting a new approach for protecting postmenopausal women against ischaemia‐induced myocardial injury. To investigate the putative protective effects of oxytocin or oestrogen receptor agonists against myocardial injury of ovariectomized sedentary or exercised rats, female Sprague–Dawley rats assigned to sham‐operated control and ovariectomized (OVX) groups were kept sedentary or undertook swimming exercise for 4 weeks and were treated with saline, an oestrogen receptor (ER) β (DPN) or ERα agonist (PPT) or oxytocin. Ovariectomy increased weight gain and anxiety in sedentary rats, whereas exercise prevented weight gain. When accompanied by exercise, both ER agonists and oxytocin inhibited weight gain and anxiety; oxytocin, in the absence or presence of exercise, increased the left ventricular diastolic dimensions and ejection fraction, whereas ER agonists also increased left ventricular diameter when given to exercised rats. Upon the induction of myocardial ischaemia–reperfusion in the OVX rats, plasma creatine kinase‐(muscle–brain) was depressed by PPT and oxytocin, whereas DPN, PPT and OT reduced plasminogen activator inhibitor‐1 concentrations. The increased tumour necrosis factor‐α concentration in OVX rats was also suppressed by exercise or DPN, PPT or oxytocin treatments, whereas the interleukin‐6 concentration was diminished by all the treatments when given in conjunction with exercise. Disorganization of cardiac muscle fibres was reduced in all exercised rats. Oestrogen receptor agonists, as well as oxytocin, in conjunction with exercise may be effective new therapeutics to protect against myocardial ischaemia in postmenopausal women.