Acid sphingomyelinase/ceramide mediates arterial angiotensin II-induced endothelial dysfunction

AIM To investigate the effect and mechanism of acid sphingomyelinase (ASM)/ceramide (Cer) pathway in arterial endothelial dysfunction caused by angiotensin II (AngII). METHODSWestern blot, real-time polymerase chain reaction (RT-PCR) and immunohistochemistry were carried out to examine the content of ASM, Cer, total endothelial nitric oxide synthase (t-eNOS) and phosphorylated eNOS (p-eNOS). Isometric force recording system was used to detect vascular function. Dihydroethidium (DHE) fluorescent probe was used to evaluate the level of superoxide anion (O-2·) in arteries. RESULTSAfter incubation with AngII (100 nmol/L), the vasodilation response of aorta to acetylcholine (Ach) decreased significantly (P<0.05), which was dose dependent, whereas vasodilation response to sodium nitroprusside (SNP) did not change. ASM protein and Cer level were increased significantly by AngII incubation compared with the control level (P<0.05), which could be reduced by incubation with desipramine (Dpm), a specific ASM inhibitor. Dpm pretreatment significantly increased the vasodilation response to Ach. AngII could significantly reduce p-eNOS content of artery as well as increase the level of O-2·, whereas Dpm could increase p-eNOS and lower the level of O-2·. CONCLUSIONAngII induces endothelial dysfunction through ASM/Cer, which might inhibit the phosphorylation of eNOS and enhance the content of O-2·.