Endogenous nitric oxide activation protects against cigarette smoking induced apoptosis in endothelial cells

Abstract
Cigarette‐induced endothelial dysfunction could be an early mediator of atherosclerosis. In this study, we explored the mechanisms of cigarette smoke extract (CSE)‐induced human aortic endothelial cells (HAEC) apoptosis. We found that 10–65% of HAECs underwent apoptotic changes when HAECs were exposed to 0.001–0.02 cigarette equivalent unit of CSE for 4 h. CSE activated the caspases‐3 and 8, the p38 MAP kinase and stress activated protein kinase/c‐Jun N‐terminal protein kinase (SAPK/JNK). Specific inhibitors of p38 MAP or SAPK/JNK reduced CSE‐induced caspase activation. We further showed that eNOS pre‐activation by l‐arginine reduced endothelial apoptosis from 65% to 5%; and eNOS inhibition by N‐ω‐nitro‐l‐arginine methyl ester accentuated CSE‐induced endothelial apoptosis. We suggest that appropriate endogenous NO production may be an important protective mechanism against smoking‐induced endothelial damage.