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

Abstract

Background: Chronic e-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 N G -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.

Evidence of premature vascular dysfunction in young adults who regularly use e-cigarettes and the impact of usage length

“…In addition, other critical mediators including prostaglandins and EDHF [ 52 ] are also involved in the endothelial-mediated response of the small vessels and may be also impaired in those that consume e-cigarettes, as suggested by our data from the PORH, LTH and iontophoresis with ACh reactivity tests. Our results support reduced endothelial-dependent microvascular function which was described in another cohort of users of e-cigarettes [ 19 ]. Recently, a study completed in a preclinical model exposed to e-cigarette vapor has also identified impaired endothelial-independent mechanisms [ 53 ].…”

“…It is well established that traditional combustible tobacco usage is associated with worse endothelial function and lowered nitric oxide levels [ 49 – 51 ]. Preliminary evidence in the microvasculature [ 19 ] and other vascular beds [ 12 ] supports that e-cigarette use also leads to a reduction of this mediator [ 12 ]. Our results align with previous observations and support that regular consumers of e-cigarettes exhibit a reduction of this essential vasodilator also in the microcirculation, as evaluated through LTH.…”

“…In fact, microvascular dysfunction is a crucial mechanism in the development and progression of cardiovascular disease and often precedes other macrovascular pathological processes [ 17 , 18 ]. A recent study has shown reduced microvascular function, particularly endothelium-dependent, in chronic users of e-cigarettes [ 19 ]. Despite these early findings, the regular effects of e-cigarette usage on vascular function are still not yet well understood.…”

Coding Hypertension by Nicotine: Unraveling the Sex-Specific Role Of m6A Demethylase for NOX2 RNA-Protein Connection

“…In contrast, no significant effects were observed in male vapers. 14 Of course, vaping/smoking cessation is and will remain the most potent approach to prevent cardiovascular and respiratory side effects.…”