The Cardioprotective Effect of a Statin and Cilostazol Combination: Relationship to Akt and Endothelial Nitric Oxide Synthase Activation

Background Atorvastatin (ATV) protects against ischemia-reperfusion by upregulating Akt and subsequently, endothelial nitric oxide synthase (eNOS) phosphorylation at Ser-1177. However, when given orally, high doses of ATV (10 mg/kg/d) are needed to achieve maximal protective effect in the rat. Protein kinase A (PKA) also phosphorylates eNOS at Ser-1177. As PKA activity depends on cAMP, cilostazol (CIL), a phosphodiesterase type III inhibitor, may stimulate NO production by activating PKA. Hypothesis: CIL and ATV may have synergistic effects on eNOS phosphorylation and myocardial infarct size (IS) reduction.