Abstract: OBJECTIVE:To evaluate whether endothelial dysfunction and hypertension are prevented by trans-cinnamaldehyde(t CA) through the activation of endothelial nitric oxide synthase(e NOS).METHODS:Human umbilical vein endothelial cells(HUVECs) were cultured in vitro and stimulated with t CA to determine cell viability using the methyl thiazolyl tetrazolium assay.The effect of t CA on nitric oxide(NO) production was determined by diaminofluorescein-dyes in the absence or presence of inhibitors of e NOS,AMPK,PKA,and AKT.The effect of t CA on blood pressure was determined by the tail-cuff method in obesity spontaneous hypertension(SHR.Cg-Leprcp/NDmcr) rats.The phosphorylation of e NOS and protein expression of the insulin-signaling pathway(Ins R-IRS1-PI3 K-AKT)were measured by western blot.RESULTS:t CA at concentrations less than 100 μM did not affect cell viability in cultured HUVECs.Stimulation with t CA promoted NO release in a time-dependent manner compared with the control group.t CA-treated HUVECs also significantly increased AKT-Ser473 and e NOS-Ser1177 phosphorylation.In SHR-CP rats,treatment with t CA at a dose of 40 mg/kg/day for 6 weeks markedly reduced the systolic blood pressure and diastolic blood pressure,increased the phosphorylation of AKT and e NOS,and increased urinary nitric oxidation.CONCLUSION:t CA attenuated endothelial dysfunction and reduced blood pressure in SHR-CP rats.The underlying mechanisms may involve the increase in AKT and e NOS phosphorylation and the release of e NOS-derived NO.

Key words: trans-cinnamaldehyde, nitric Oxide, eNOS, hypertension, HUVEC