The Cardioprotection Of FLNT Against Myocardium Ischemia/reperfusion Injury

Aim: to investigate the cardioprotection of N—2-(acetylferulamidoethyl)nitrate(FLNT) against myocardium ischemia/reperfusion(I/R) injury and the possible mechanismMethods: Three varieties of animal experimental models were successfully made: myocardium ischemia/reperfusion (I/R), late ischemia preconditioning (LPC) and vessel tension in vitro. The makers of cardioprotection against myocardium I/R damage were investigated. The vessel tension was investigated to study the vasorelaxation effect of FLNT in vitro. And the the blockers of guanylate cyclase(GC) and potassium channels were used to study the possible mechanism of vasoreactivity. The serum and urine were analysed through HPLC-MS-MS to identify the possible metabolites of FLNT in rats. And the activity of the major metabolite DFNT on the cardioprotection against myocardium I/R injury and its vasoactiviry was also investigated.Results: FLNT could protect rats myocardium against I/R through the stragies of treatment and preconditioning. It diminished the infarct size, reduced the level of creatine kinase(CK) and lactate dehydrogenase (LDH). FLNT increase the level of NO in heart tissue, reduced the level of maleic dialdehyde (MDA). FLNT also could induce late ischemia preconditioning in rats, it diminished myocardium infarct size, reduced the level of CK and LDH, increased the level of Mn-SOD and Bcl-2/Bax in heart tissue after I/R procedure, which strengthen the potency of anti-oxidant and anti-apoptosisasis, It increase the level of induced nitric oxide synthase in heart tissues without I/R procedure, which supples the effect media of LPC.FLNT could relax the peripheril vessels and coronary artery. The relaxation on arteries was endothium-independent. The blocker of guanylate cyclase(GC) could diminish the relaxation of FLNT.The metabolites of FLNT included two varaties: nitro group free metabolites and acetyl group free metabolites. The major acetyl group free metabolite (N-2-(ferulamidoethyl)nitrate(DFNT) had the activity of cardioprotection against I/R and vasorelaxation.Conclusion: FLNT had the activities of protecting myocardium against I/R injury through pathways of treatment and ischemia proconditioning. The machanis was possibly related to its characteristics of anti-oxidant, anti-apoptosis. It could relax peripheral artery and coronary artery possibly by stimulating GC and opening potassium channels as nitric oxide donor. Its major acetyl group free metabolite DFNT had the activities of cardioprotection against myocardium I/R injury and vasorelaxation.