Proponents for electronic cigarettes (E-cigs) claim that they are a safe alternative to tobacco-based cigarettes; however, little is known about the long-term effects of exposure to E-cig vapor on vascular function. The purpose of this study was to determine the cardiovascular consequences of chronic E-cig exposure. Female mice (C57BL/6 background strain) were randomly assigned to chronic daily exposure to E-cig vapor, standard (3R4F reference) cigarette smoke, or filtered air ( n = 15/group). Respective whole body exposures consisted of four 1-h-exposure time blocks, separated by 30-min intervals of fresh air breaks, resulting in intermittent daily exposure for a total of 4 h/day, 5 days/wk for 8 mo. Noninvasive ultrasonography was used to assess cardiac function and aortic arterial stiffness (AS), measured as pulse wave velocity, at three times points (before, during, and after chronic exposure). Upon completion of the 8-mo exposure, ex vivo wire tension myography and force transduction were used to measure changes in thoracic aortic tension in response to vasoactive-inducing compounds. AS increased 2.5- and 2.8-fold in E-cig- and 3R4F-exposed mice, respectively, compared with air-exposed control mice ( P < 0.05). The maximal aortic relaxation to methacholine was 24% and 33% lower in E-cig- and 3R4F-exposed mice, respectively, than in controls ( P < 0.05). No differences were noted in sodium nitroprusside dilation between the groups. 3R4F exposure altered cardiac function by reducing fractional shortening and ejection fraction after 8 mo ( P < 0.05). A similar, although not statistically significant, tendency was also observed with E-cig exposure ( P < 0.10). Histological and respiratory function data support emphysema-associated changes in 3R4F-exposed, but not E-cig-exposed, mice. Chronic exposure to E-cig vapor accelerates AS, significantly impairs aortic endothelial function, and may lead to impaired cardiac function. The clinical implication from this study is that chronic use of E-cigs, even at relatively low exposure levels, induces cardiovascular dysfunction. NEW & NOTEWORTHY Electronic cigarettes (E-cigs) are marketed as safe, but there has been insufficient long-term exposure to humans to justify these claims. This is the first study to report the long-term in vivo vascular consequences of 8 mo of exposure to E-cig vapor in mice (equivalent to ~25 yr of exposure in humans). We report that E-cig exposure increases arterial stiffness and impairs normal vascular reactivity responses, similar to other risk factors, including cigarette smoking, which contribute to the development of cardiovascular disease.

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BackgroundResistance training (RT) enhances muscle protein synthesis and hypertrophy while increasing strength and power. Some multi-ingredient performance supplements (MIPS) have been shown to augment the physiological improvements associated with RT. The purpose of this study was to investigate the impact of specific pre- and post-workout MIPS on anabolic hormones, body composition, muscle strength, and power in resistance-trained men participating in a periodized RT program.MethodsTwenty-four ( mean ± SE; 24.0 ± 0.9 years; 180.5 ± 5.8 cm; 83.7 ± 0.5 kg) resistance-trained men completed 6 wks of periodized RT (3x/wk). Participants were assigned to one of two groups based upon maximal voluntary contraction of the quadriceps (Biodex) to lean mass (LM) ratio. Group 1 (n = 13; MIPS) consumed one serving of NO-Shotgun® (whey protein, casein protein, branched-chain amino acids, creatine, beta alanine, and caffeine) before each workout and one serving of NO-Synthesize® (whey protein, casein protein, branched-chain amino acids, creatine, and beta alanine; Vital Pharmaceuticals, Inc., Davie, FL) immediately after each workout and on non-RT days. Group 2 (n = 11; Placebo; PLA) consumed a flavor-matched isocaloric maltodextrin placebo. Serum insulin-like growth factor 1, human growth hormone, testosterone, body composition (DXA), circumferences, 1-repetition maximal strength (1RM) of the upper (chest press) and lower body (leg press), and anaerobic power (Wingate test) were assessed before and after the intervention. Statistical analysis included a 2 × 2 (group x time) ANOVA with repeated measures. Tukey LSD post hoc tests were used to examine pairwise differences. Significance was set at p < 0.05.ResultsThere was a main time effect (p = 0.035) for testosterone to increase, but no differences between groups were observed. There were no differences in the other blood hormones. Group x time interactions were observed for LM (MIPS: PRE, 62.9 ± 2.1 to POST, 65.7 ± 2.0 vs. PLA: PRE, 63.5 ± 2.3 to POST, 64.8 ± 2.5 kg; p = 0.017). Only a main effect of time was noted for circumference measures. Both groups increased upper and lower body 1RM strength to a similar degree. MIPS significantly increased peak anaerobic power (PRE, 932.7 ± 172.5 W vs. POST, 1119.2 ± 183.8 W, p = 0.002) while PLA remained unchanged (PRE, 974.4 ± 44.1 W vs. POST, 1033.7 ± 48.6 W, p = 0.166).ConclusionConsumption of MIPS during the course of a periodized RT program facilitated training-induced improvement in LM in trained males, whereas the consumption of PLA did not. MIPS improved measures of anaerobic power while PLA did not.

Pulmonary exposure to multiwalled carbon nanotubes (MWCNTs) disrupts peripheral microvascular function. Thrombospondin-1 (TSP-1) is highly expressed during lung injury and has been shown to alter microvascular reactivity. It is unclear exactly how TSP-1 exerts effects on vascular function, but we hypothesized that the TSP-1 receptor CD47 may mediate changes in vasodilation. Wildtype (WT) or CD47 knockout (CD47 KO) C57B6/J-background animals were exposed to 50 µg of MWCNT or saline control via pharyngeal aspiration. Twenty-four hours postexposure, intravital microscopy was performed to assess arteriolar dilation and venular leukocyte adhesion and rolling. To assess tissue redox status, electron paramagnetic resonance and NOx measurements were performed, while inflammatory biomarkers were measured via multiplex assay.Vasodilation was impaired in the WT + MWCNT group compared with control (57 ± 9 vs 90 ± 2% relaxation), while CD47 KO animals showed no impairment (108 ± 8% relaxation). Venular leukocyte adhesion and rolling increased by >2-fold, while the CD47 KO group showed no change. Application of the antioxidant apocynin rescued normal leukocyte activity in the WT + MWCNT group. Lung and plasma NOx were reduced in the WT + MWCNT group by 47% and 32%, respectively, while the CD47 KO groups were unchanged from control. Some inflammatory cytokines were increased in the CD47 + MWCNT group only. In conclusion, TSP-1 is an important ligand mediating MWCNT-induced microvascular dysfunction, and CD47 is a component of this dysregulation. CD47 activation likely disrupts nitric oxide (•NO) signaling and promotes leukocyte-endothelial interactions. Impaired •NO production, signaling, and bioavailability is linked to a variety of cardiovascular diseases in which TSP-1/CD47 may play an important role.

Pulmonary exposure to multi-walled carbon nanotubes (MWCNT) has been shown to disrupt endothelium-dependent arteriolar dilation in the peripheral microcirculation. The molecular mechanisms behind these arteriolar disruptions have yet to be fully elucidated. The secreted matricellular matrix protein thrombospondin-1 (TSP-1) is capable of moderating arteriolar vasodilation by inhibiting soluble guanylate cyclase activity. We hypothesized that TSP-1 may be a link between nanomaterial exposure and observed peripheral microvascular dysfunction. To test this hypothesis, wild-type C57B6J (WT) and TSP-1 knockout (KO) mice were exposed via lung aspiration to 50 μg MWCNT or a Sham dispersion medium control. Following exposure (24 h), arteriolar characteristics and reactivity were measured in the gluteus maximus muscle using intravital microscopy (IVM) coupled with microiontophoretic delivery of acetylcholine (ACh) or sodium nitroprusside (SNP). In WT mice exposed to MWCNT, skeletal muscle TSP-1 protein increased > fivefold compared to Sham exposed, and exhibited a 39% and 47% decrease in endothelium-dependent and -independent vasodilation, respectively. In contrast, TSP-1 protein was not increased following MWCNT exposure in KO mice and exhibited no loss in dilatory capacity. Microvascular leukocyte–endothelium interactions were measured by assessing leukocyte adhesion and rolling activity in third order venules. The WT+MWCNT group demonstrated 223% higher leukocyte rolling compared to the WT+Sham controls. TSP-1 KO animals exposed to MWCNT showed no differences from the WT+Sham control. These data provide evidence that TSP-1 is likely a central mediator of the systemic microvascular dysfunction that follows pulmonary MWCNT exposure.