Age-Dependent Effects of Remote Preconditioning in Hypertensive Rat Hearts are Associated With Activation of RISK Signaling

Abstract

Remote ischemic preconditioning (RIPC) represents one of the forms of innate cardioprotection. While being effective in animal models, its application in humans has not been always beneficial, which might be attributed to the presence of various comorbidities, such as hypertension, or being related to the confounding factors, such as patients’ sex and age. RIPC has been shown to mediate its cardioprotective effects through the activation of Reperfusion Injury Salvage Kinase (RISK) pathway in healthy animals, however, scarce evidence supports this effect of RIPC in the hearts of spontaneously hypertensive (SHR) rats, in particular, in relationship with aging. The study aimed to investigate the effectiveness of RIPC in male SHR rats of different age and to evaluate the role of RISK pathway in the effect of RIPC on cardiac ischemic tolerance. RIPC was performed using three cycles of inflation/deflation of the pressure cuff placed on the hind limb of anesthetized rats aged three, five and eight months. Subsequently, hearts were excised, Langendorff-perfused and exposed to 30-min global ischemia and 2-h reperfusion. Infarct-sparing and antiarrhythmic effects of RIPC were observed only in three and five months-old animals but not in eight months-old rats. Beneficial effects of RIPC were associated with increased activity of RISK and decreased apoptotic signaling only in three and five months-old animals. In conclusion, RIPC showed cardioprotective effects in SHR rats that were partially age-dependent and might be attributed to the differences in the activation of RISK pathway and various aspects of ischemia/reperfusion injury in aging animals.