Interaction of exercise and simvastatin on myocardial ischemia‐reperfusion (I‐R) injury: Role of nitric oxide.

Abstract

The interaction of statins and exercise are not well known, yet they are often co-prescribed for cardiovascular health. Here we investigate the interaction of simvastatin (SIM) and exercise on myocardial tolerance to I-R. Female rats (22–25/gp) were sedentary control (S), fed 10 mg SIM/kg/day (SD), exercised on a treadmill (70% VO2max, 60 min/d, 5 d/wk) (R), or fed SIM + exercise (RD) for 4 wks. Isolated perfused working hearts were subjected to 30 min ischemia then reperfused. Some were perfused with 100 μM L-NAME to prevent nitric oxide involvement. I-R recovery of pre-ischemic cardiac external work was 17.6±6.6% in S. Recovery was higher (P<0.05) in SD (37.7±7.7%) and R (40.1±7.7%) and tended to be highest in RD (49.7±7.1%). Recovery was not improved further by supplementing RD with Coenzyme Q (CoQ) to replace CoQ lost by SIM treatment. Compared to S, LDH release during reperfusion was decreased in SD, R, and RD by similar amounts. LDH release was lowest of all in RD+CoQ. Although eNOS expression was similar among groups, L-NAME abrogated protection in SD, but did not attenuate protection in R or RD. Only SIM treatment increased prostaglandin production and only exercise increased HSP72 content. We conclude that NO is a critical mediator of statin-induced protection, but not exercise-induced protection. Also, combining the treatments may provide more protection than either alone. Supported by AHA-Texas Affiliate.