Myocardial Preconditioning Potential of Hedgehog Activator Purmorphamine (Smoothened Receptor Agonist) against Ischemia-Reperfusion in Deoxycortisone Acetate Salt-Induced Hypertensive Rat Hearts

Abstract

Aim: To investigate the myocardial preconditioning potential of hedgehog activator smoothened (SMO) receptor agonist purmorphamine (PUR) against ischemia-reperfusion (I/R) injury in deoxycortisone acetate (DOCA) salt-induced hypertensive rat heart. Methods: Hypertension in rats was produced by surgical removal of the kidney and DOCA salt administration for 6 weeks. Isolated rat heart was subjected to 30 min ischemia followed by 120 min of I/R. The heart was subjected to pharmacological preconditioning with the hedgehog (Hh) activator PUR (1 μM), PUR (2 μM), and atractyloside (4 μM), an mPTP opener, in the last episode of reperfusion before I/R. Elevated blood pressure was evaluated through tail-cuff method. Myocardial infarction was assessed in terms of the increase in lactate dehydrogenase, creatinine kinase-muscle/brain, and infarct size through triphenyltetrazolium chloride staining. Further, there were a decrease in the release of nitrite and coronary flow rate. Immunohistochemistry was performed for the assessment of tumor necrosis factor-α level in cardiac tissue. Results: Pharmacological preconditioning with PUR significantly attenuated I/R-induced myocardial infarction. However, atractyloside limits the ameliorative preconditioning potential of PUR and confirmed the role of Hh pathway in ischemic preconditioning. Conclusion: It may be concluded that the Hh activator PUR (SMO receptor agonist) prevents I/R injury in DOCA salt-induced hypertensive rat heart.