Sex Differences in Oxidative Stress-Mediated Reductions in Microvascular Endothelial Function in Young Adult e-Cigarette Users

Abstract

BACKGROUND: Chronic electronic-cigarette (EC) use is reported to decrease vascular endothelial function. However, the mechanism(s) mediating this reduction remain unclear. In this study, we examined endothelium- and NO-dependent dilation, and the role of oxidative stress in attenuating these responses, in healthy young EC users (n=20, 10 males/10 females) compared with healthy controls (n=20, 10 males/10 females). We hypothesized that EC would have reduced endothelium- and NO-dependent dilation and administration of the superoxide scavenger tempol would increase these responses in EC. We further hypothesized that female EC would have the greatest reductions in endothelium- and NO-dependent dilation. METHODS: We assessed microvascular endothelium-dependent vasodilator function in vivo by measurement of cutaneous vascular conductance (%CVCmax) responses to a standardized local heating protocol in control and 10 μM tempol-treated sites. After full expression of the local heating response, 15 mM NG-nitro-L-arginine methyl ester (NO synthase inhibition) was perfused. RESULTS: EC had significantly reduced endothelium- (73±15 versus 87±9%CVCmax; P<0.001) and NO-dependent (48±17% versus 62±15%; P=0.011) dilation. Tempol perfusion increased endothelium-dependent (84±12%CVCmax P=0.01) and NO-dependent (63±14% P=0.005) dilation in EC but had no effect in healthy control. Within female sex, EC had lower endothelium-dependent (71±13 versus 89±7%CVCmax; P=0.002) and NO-dependent (50±6 versus 69±11%; P=0.005) dilation compared with healthy control, and tempol augmented endothelium-dependent (83±13%CVCmax; P=0.002) and NO-dependent (62±13%; P=0.015) dilation. There were no group or treatment differences within male sex. CONCLUSION: Healthy young adult EC users have reduced microvascular endothelium-dependent and NO-dependent dilation, driven by greater reductions in female EC users, and mediated in part by superoxide.