Short-term effects of electronic cigarettes on cerebrovascular function: A time course study.

NEW FINDINGS: What is the central question of this study? Acute exposure to electronic cigarettes (Ecigs) triggers abnormal vascular responses in systemic arteries; however, effects on cerebral vessels are poorly understood and time for recovery is not known. We hypothesized that exposure to cigarettes or Ecigs would trigger rapid (<4 h) impairment of the middle cerebral artery (MCA) but that this would resolve by 24 h. What is the main finding and its importance? Cigarettes and Ecigs caused similar degree and duration of MCA impairment. We find it takes ~72 hours after exposure for MCA function to return to normal. This suggests that Ecig use is likely to produce similar adverse vascular health outcomes to those seen with cigarette smoke. ABSTRACT: Temporal influences of electronic cigarettes (Ecigs) on blood vessels are poorly understood. In this study, we evaluated a single episode of cigarette versus Ecig exposure on middle cerebral artery (MCA) reactivity and determined how long after the exposure MCA responses took to return to normal. We hypothesized that cigarette and Ecig exposure would induce rapid (<4 h) reduction in MCA endothelial function and would resolve within 24 h. Sprague-Dawley rats (4 months old) were exposed to either air (n = 5), traditional cigarettes (20 puffs, n = 16) or Ecigs (20-puff group, n = 16; or 60-puff group, n = 12). Thereafter, the cigarette and Ecig groups were randomly assigned for postexposure vessel myography testing on day 0 (D0, 1-4 h postexposure), day 1 (D1, 24-28 h postexposure), day 2 (D2, 48-52 h postexposure) and day 3 (72-76 h postexposure). The greatest effect on endothelium-dependent dilatation was observed within 24 h of exposure (∼50% decline between D0 and D1) for both cigarette and Ecig groups, and impairment persisted with all groups for up to 3 days. Changes in endothelium-independent dilatation responses were less severe (∼27%) and shorter lived (recovering by D2) compared with endothelium-dependent dilatation responses. Vasoconstriction in response to serotonin (5-HT) was similar to endothelium-independent dilatation, with greatest impairment (∼45% for all exposure groups) at D0-D1, returning to normal by D2. These data show that exposure to cigarettes and Ecigs triggers a similar level/duration of cerebrovascular dysfunction after a single exposure. The finding that Ecig (without nicotine) and cigarette (with nicotine) exposure produce the same effects suggesting that nicotine is not likely to be triggering MCA dysfunction, and that vaping (with/without nicotine) has potential to produce the same vascular harm and/or disease as smoking.

RAGE and AXL expression following secondhand smoke (SHS) exposure in mice.

Aim and Purpose: Tobacco exposure is one of the top three global health risks leading to the development of chronic obstructive pulmonary disease (COPD). Although there is extensive research into the effects of cigarette smoke, the effect of secondhand smoke (SHS) in the lung remains limited. SHS induces receptors for advanced glycation end-products (RAGE) and an inflammatory response that leads to COPD characteristics. Semi-synthetic glycosaminoglycan ethers (SAGEs) are sulfated polysaccharides derived from hyaluronic acid that inhibit RAGE signaling. The growth arrest-specific 6 (Gas6) protein is known to induce dynamic cellular responses and is correlated with cell function. Gas6 binds to the AXL tyrosine kinase receptor and AXL-mediated signaling is implicated in proliferation and inflammation. This project's purpose was to study the correlation between RAGE, AXL, and Gas6 during SHS exposure in the lung. Methods: C57Bl/6 mice were exposed to SHS alone or SHS + SAGEs for 4 weeks and compared to control animals exposed to room air (RA). Results: Compared to controls we observed: 1) increased RAGE mRNA and protein expression in SHS-exposed lungs which was decreased by SAGEs; 2) decreased expression of total AXL, but highly elevated pAXL expression following exposure; 3) highly elevated Gas6 expression when RAGE was targeted by SAGEs during SHS exposure; 4) SHS-mediated BALF cellularity and inflammatory molecule elaboration; and 5) the induction of both RAGE and AXL by Gas6 in cell culture models. Conclusions: Our results suggest that there is a possible correlation between RAGE and AXL during SHS exposure. Additional research is critically needed that dissects the molecular interplay between these two important signaling cascades. At this point, the current studies provide insight into tobacco-mediated effects in the lung and clarify possible avenues for alleviating complications that could arise during SHS exposure such as those observed during COPD exacerbations.