Sex differences in oxidative stress-mediated reductions in microvascular endothelial function in young e-cigarette users

Abstract

Tobacco and nicotine use cause vascular endothelial dysfunction, increasing lifetime cardiovascular disease risk. Chronic e-cigarette use is reported to decrease endothelial function, however the mechanism(s) mediating this reduction remain unclear. Using the cutaneous circulation as a model, we examined endothelium- and nitric oxide (NO)-dependent dilation, and the role of oxidative stress in attenuating these responses, in otherwise healthy, young chronic (≥6 months) e-cigarette users (EC) compared to healthy controls (HC). We hypothesized that: EC would have reduced endothelium- and NO-dependent dilation, and local tempol (superoxide scavenger) administration would increase these responses in EC. We further examined the effect of sex within HC and EC and hypothesized that female EC would have the greatest reduction in endothelium- and NO-dependent dilation. 20 HC (21±2 yrs; 10M/10F) and 18 EC (21±2 yrs; 10M/8F) underwent a standard local heating protocol (42°C; 0.1°C·s-1). Two intradermal microdialysis fibers were placed in the ventral forearm skin for local delivery of lactated Ringer’s (control), or 10μM tempol. After full expression of the local heating response, 15mM NG-nitro-L-arginine methyl ester (L-NAME; NO synthase-inhibition) was perfused. Red cell flux was measured continuously by laser-Doppler flowmetry, and cutaneous vascular conductance (CVC=flux/MAP) was standardized to maximum (%CVCmax; 28mM SNP + 43°C). Between groups, endothelium- (EC: 73 ± 15 vs HC: 87 ± 9 %CVCmax; p<0.001) and NO-dependent (EC: 48.1± 17.0% vs. HC: 61.8 ± 14.7%; p=0.011) dilation were attenuated in EC compared to HC. Local tempol perfusion increased endothelium- (83.8 ±12.1% p=0.007) and NO-dependent (61.4 ± 14.2% p=0.011) dilation in EC but had no effect in HC (all p>0.05). Within sex, female EC had lower endothelium- (EC: 69.9±3.4 vs HC: 89.1±3.5 %CVCmax; p<0.001) and NO-dependent (EC: 46.9±5.5 vs HC: 69.4±5.0%; p=0.005) dilation compared to female HC, but there were no differences between these responses in HC and EC males (both p>0.05). Tempol perfusion augmented endothelium- (83.4±4.4 %CVCmax; p=0.31) and NO-dependent (60.2±5.1%; p=0.04[AS1] ) dilation in EC females but had no effect in EC males (both p>0.05). These data suggest that otherwise healthy young adult e-cigarette users have reduced microvascular endothelium- and NO-dependent dilation. Within e-cigarette users, these results are driven by greater reductions in females, and superoxide contributes to these impairments. Supported by NIEHS/NIH P30 ES005605 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.