Abstract 3313: Smoking Abolishes Ischemic Preconditioning-Induced Augmentation of Endothelium-Dependent Vasodilation: Role of Endothelium-Derived Nitric Oxide and Circulating Endothelial Progenitor Cells
Background: Several studies have shown that both early and late effects of ischemic preconditioning (IPC) protect against myocardial injury following ischemic reperfusion. Recently, we have shown that repetition of IPC stimulus augments endothelium-dependent vasodilation in forearm circulation of healthy subjects through increases in nitric oxide (NO) production and number of endothelial progenitor cells (EPCs) under a local condition. The purpose of this study was to evaluate the late effects of IPC on endothelial function in smokers.
Methods and Results: Late phase of IPC was induced by upper limb ischemia (cuff inflation of over 200 mmHg for 5 minutes) six times a day for one month. We evaluated forearm blood flow (FBF) responses to acetylcholine (ACh) and to sodium nitroprusside (SNP) before and after IPC stimulus in 15 male smokers (27±7 yr) and 15 male non-smokers (26±5 yr). FBF was measured using a strain-gauge plethysmography. The IPC stimulus significantly increased plasma concentration of vascular endothelial growth factor (VEGF) from 84.7±10.6 to 120.3±13.5 pg/mL (P<0.05), circulating level of EPCs from 1258±198 to 1608±183 cells/mL (P<0.05) and FBF responses to ACh from 17.3±4.9 to 24.8±6.9 mL/min/100 mL tissue (P<0.05) in non-smokers, but these did not change in the smoker group. The FBF responses to SNP were similar before and after the IPC stimulus. Infusion of NG-monomethyl-L-arginine, a NO synthase inhibitor, completely eliminated the IPC stimulus-induced augmentation of FBF responses to ACh in non-smokers.
Conclusions: These findings suggest that repetition of IPC stimulus may be a simple, safe, and feasible therapeutic technique for endothelial protection of peripheral vessels. However, smoking abolishes repetition of IPC stimulus-induced augmentation of endothelium-dependent vasodilation.