Khori V, Shirmohammali H, Alizadeh A M, rajaii M, Banikarimi A, Molseghi M. Role of mineralocorticoid receptors in the mediation of acute effects of hydrocortisone in isolated ischemic rat heart. Physiol Pharmacol 2013; 17 (2) :137-147
URL:
http://ppj.phypha.ir/article-1-899-en.html
Abstract: (11369 Views)
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 μM). 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.