The Effects of E-Cigarette Exposure on the Peripheral Vasculature

Abstract

The Effects of E-Cigarette Exposure on the Peripheral Vasculature Christopher Pitzer E-cigarettes have emerged as popular alternatives to traditional smoking, partially because of efforts of manufacturers to portray them as safe. Recent studies have cast doubt on claims of safety, our lab has published data showing a significant impairment in endothelium-dependent dilation with chronic exposure, however the acute temporal effects and mechanisms involved with E-cigarette exposure on the vasculature are still poorly characterized. This study uses an intravital microscopy approach to evaluate the effects of acute time course changes following E-cigarette vapor exposure on second-order arterioles in the gluteus maximus muscle of mice. We hypothesized that endothelial impairment would be observed with a single E-cigarette exposure. C57BL/6 mice were anesthetized and a portion of the gluteus maximus muscle was externalized to allow visualization of second order arterioles. Arteriolar tone was monitored for up to 120-minutes in one study to determine the effects of E-cigarette exposure. In a separate study, vascular function was assessed by dilation to acetylcholine 50 minutes after exposure to a single 5-minute (10 puff) exposure to E-cigarette vapor. Significant vasoconstriction occurred in E-cigarette exposed animals with or without nicotine using 50:50 vegetable glycerin/propylene glycol (VG/PG-18 and VG/PG-0, respectively, p<0.05), as well as in animals exposed to 100% PG with no nicotine (PG-0) and 100% VG with no nicotine (VG-0). E-cigarette responses were similar to animals exposed to traditional tobacco-based 3R4F reference cigarette (3R4F). No significant differences in vessel response to acetylcholine prevs. postexposure were generally found; except with VG/PG-18, which showed significant increase in acetylcholine curve slope after vaping. Assessment of growth factor and cytokines response following chronic (8-month) exposure to E-cigarette exposure was obtained from a separate study which we have previously show impaired vascular function (Olfert et al. 2018). Cytokine quantification was performed using a multiplex kit from Meso-Scale Discovery (Rockville, MD, US) on homogenates of lung, gastrocnemius muscle, serum and bronchoalveolar lavage fluid (BALF) in C57BL/6 mice exposed to filtered room air (AIR), 3R4F cigarette, and Cappuccinoflavored E-cigarette vapor (E-CIG, 50:50 VG/PG). IL-6 in the serum of E-CIG animals was significantly lower than AIR animals (P<0.05). VEGF tended to be lower in BALF and lungs of ECIG animals relative to air controls. Granulocyte-macrophage colony stimulating factor (GMCSF) also tended to be lower in E-CIG animals relative to 3R4F and AIR animals. Collectively, our data shows that acute E-cigarette exposure causes peripheral constriction (~20%) of blood vessels independent of nicotine and suggests that the base components of E-liquid cause vasoconstriction to a similar degree. Endothelial dilatory capacity is largely unaffected by Ecigarette exposure after 1-hour following a single acute exposure. Chronic E-cigarette exposure alters the expression of IL-6 in the serum and may affect expression of VEGF in the lungs and BALF and GM-CSF expression in the lungs. Taken together these data suggest that vaping has acute effects on the basal blood vessel tone that is similar to traditional cigarettes, suggesting the chronic E-cigarette use is likely to produce long-term vascular health consequences similar to that observed with cigarette smoking.