Cardioprotective effects of low-dose combination therapy with rosuvastatin and fasudil in the isolated rat heart.

The cardiovascular pleiotropic effects of statins and a Rho-kinase inhibitor (fasudil) could be of interest to prevent myocardial ischemia reperfusion injury (MIRI). In the present study, we investigated whether low-dose rosuvastatin and fasudil, separately not possessing cardioprotection, express cardioprotective effects when combined. The isolated rat hearts underwent 30 min global ischemia and 120 min reperfusion. Rosuvastatin (3 microM) and fasudil (1 microM) were administered 15 min before ischemia. NG-nitro-L-arginine methylester (30 microM) (L-NAME) was given at the onset of reperfusion. Myocardial infarct size, apoptosis, myocardial nitric oxide (NO) content and endothelial nitric oxide synthase (eNOS) expression were evaluated. The combination treatment significantly decreased infarct size and percentage of apoptosis and increased the content of NO and eNOS expression, whereas treatment with rosuvastatin and fasudil alone at the same doses did not lead to cardioprotection. Furthermore, L-NAME reversed the cardioprotective effect of rosuvastatin/fasudil combination treatment. In summary, rosuvastatin combined with fasudil treatment had synergistic protective effects against MIRI, which were mediated by increasing eNOS and NO production. This new concept could be valuable in MIRI prevention.