Increased nitric oxide bioavailability in endothelial cells contributes to the pleiotropic effect of cerivastatin

Article

关键词: DIETARY L-ARGININE;    SUPEROXIDE;    RELEASE;    ATHEROSCLEROSIS;   

DOI  :  10.1161/hc0802.104283

来源: SCIE

【 摘 要 】

Background-Although statins preserve endothelial function by reducing serum cholesterol levels, it has been suggested they may also stimulate nitric oxide (NO) synthase in endothelium with concurrent increase in superoxide (O-2(-)) generation, leading to impairment of NO activity. Therefore, measurements of biologically active NO and O-2(-) in endothelium after exposure to the HMG-CoA reductase inhibitor cerivastatin were undertaken to evaluate its potential effect on NO biological activity. Methods and Results-Highly sensitive electrochemical NO and O-2(-) microsensors were placed near the surface of a single human umbilical vein endothelial cell, and the kinetics of NO and O-2(-) release were recorded in vitro. Cerivastatin demonstrated a time-dependent effect on NO release in endothelial cells. The initial release (approximately the first 3 minutes) was concentration-dependent (0.01 to 10 mumol/L) and was similar to that observed for typical NO synthase agonists calcium ionophore or acetylcholine. Cerivastatin stimulated NO release at a favorable rate and scavenged O-2(-), which led to the preservation of the active concentration of NO. The sustained effect (after approximate to6 hours) of cerivastatin on endothelium was associated with an approximate to35% increase in NO release as compared with the initial effect. In contrast to the initial effect, the sustained effect of cerivastatin was shown at concentrations approximate to100-fold lower and was dependent on inhibition of endothelial HMG-CoA reductase. Conclusions-These data provide direct evidence to prove that in the presence of cerivastatin, the NOS system in endothelium operates with high efficiency toward increasing NO activity by activation of NO release and by concurrent inactivation of O-2(-).

【 授权许可】

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