Role of mineralocorticoid receptors in the mediation of acute effects of hydrocortisone in isolated ischemic rat heart

Introduction: Cardiac preconditioning is an important method to reduce the damage caused by prolonged ischemia. Previous studies have shown that corticosteroids have protective effects on the heart, however at high concentrations this effect may be reduced with unknown mechanisms. We hypothesize that the contradictory effects of hydrocortisone at high concentration may be mediated via mineralocorticoid receptors. Therefore, this study was designed to determine the protective effects of various concentrations of hydrocortisone on the heart and its relationship with the mineralocorticoid receptor. Methods: In an experimental study, ninety-six male rats were divided into eight groups treated with different doses of hydrocortisone (1, 5, 10 and 20 mu M). Spirinolactone was used as a mineralocorticoid receptor antagonist to investigate its role in the hydrocortisone acute effects on the heart. The hearts were excised first, and transferred and connected to the Langendorff system, and then subjected to 30 min ischemia and 90 min reperfusion. The infarct size and ventricular arrhythmias were measured. Two-way ANOVA was used to compare the groups. Results: The results showed that hydrocortisone at various concentrations could reduce the infarct size and protect cardiomyocytes. The protective effects were lower at high concentrations (P<0.05). Spironolactone, a mineralocorticoid receptor antagonist amplified these protective effects (P<0.05). Hydrocortisone and spironolactone administration not significantly decreased severity and incidence of ventricular arrhythmia in comparison with IR group (P>0.05). Conclusion: The results showed the hydrocortisone cardioprotective effects as a pharmacological preconditioning agent. Opposing effects of hydrocortisone at medium and high concentrations can at least be partially reversed by mineralocorticoid receptors.