Long-term cerebrovascular dysfunction in the offspring from maternal electronic cigarette use during pregnancy

Abstract

Electronic cigarettes (E-cigs) have been promoted as harm-free or less-risky than smoking, even for women during pregnancy. These claims are made largely on E-cig aerosol having fewer number of toxic chemicals compared to cigarette smoke. Given that even low levels of smoking are found to produce adverse birth outcomes, we sought to test the hypothesis that vaping during pregnancy (with or without nicotine) would not be harm-free, and would result in vascular dysfunction that would be evident in offspring during adolescent and/or adult life. Pregnant female Sprague Dawley rats were exposed to E-cig aerosol (1-hour/day, 5 days/week, starting on gestational day 2 until pups were weaned) using e-liquid with 0 mg/ml (E-cig0) or 18 mg/ml nicotine (E-cig18) and compared to ambient air exposed controls. Body mass at birth and at weaning were not different between groups. Assessment of middle cerebral artery (MCA) reactivity revealed a 51-56% reduction in endothelial-dependent dilation response to acetylcholine (ACh) for both E-cig0 and E-cig18 in 1-month, 3-month (adolescent), and 7-month old (adult) offspring (p<0.05 compared to air, all time points). MCA response to sodium nitroprusside (SNP) and myogenic tone were not different across groups suggesting that endothelial-independent responses were not altered. The MCA vasoconstrictor response (5-hydroxytryptamine, 5-HT) was also not different across treatment and age groups. These data demonstrate that maternal vaping during pregnancy is not harm-free and confers significant cerebrovascular health risk/dysfunction to offspring that persists into adult life.

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

“…These data are consistent with extensive literature showing that chronic nicotine administration via transdermal application does not increase the risk of cardiovascular disease (JAMA Network, 1994;Joseph et al, 1996;Meine et al, 2005;Tzivoni et al, 1998). We have also reported previously that TEMPOL is able to rescue MCA function in adolescent and adult rat offspring that have MCA dysfunction secondary to maternal Ecig exposure during pregnancy (with or without nicotine; Burrage et al, 2021). Thus, it is not immediately clear why we saw TEMPOL rescue the blunted EDD response on D1-D3 for Ecigs but not for cigarettes in the present study.…”

“…Nonetheless, a recent report (Jin et al, 2021) There is wide recognition that EVs can provide important endocrine signalling in health and disease (Stahl & Raposo, 2019). Previous work from our laboratory (Burrage et al, 2021) and others (Antoniewicz et al, 2016;Benedikter et al, 2018;Mobarrez et al, 2020) have found that Ecig exposure increases circulating EVs. Accordingly, we evaluated the temporal release of plasma EVs in our exposure groups.…”

“…Consistent with this, long‐term Ecig exposure has been shown to increase arterial stiffness and to impair (both endothelium‐dependent and ‐independent) blood vessel reactivity (El‐Mahdy et al., 2021; Franzen et al., 2018; Kerr et al., 2019; Olfert et al, 2018; Vlachopoulos et al., 2016). We have also recently reported impaired cerebrovascular endothelial function in offspring indirectly exposed (in utero) to Ecigs from maternal exposure during pregnancy (Burrage et al., 2021). Impaired cerebrovascular function is particularly concerning because it is associated with lower cerebral blood flow (Jefferson et al., 2018; Tarumi et al., 2011), neurocognitive decline (Hanon et al., 2005; Mitchell et al., 2011; Pase et al., 2016; Thorin‐Trescases et al., 2018), development of cerebral microbleeds (Ding et al., 2015) and greater overall risk for cerebrovascular and cardiovascular disease (Alzahrani et al., 2018; Mitchell, 2015), all of which are factors promoting the onset of stroke and worsening of postischaemic brain injury (Kaisar et al., 2017).…”

“…From a toxicological point of view, it is necessary to consider both the physical and chemical constituents present in the smoke/aerosol cloud delivered to the lungs. In our previous work (Burrage et al, 2021), we have reported that nearly all aerosol particles produced by Ecigs are in the fine range (<2.5 µm, PM 2.5 ) and that ∼10-20% are in the ultrafine range (<0.1 µm, PM 0.1 ). Both PM 2.5 and PM 0.1 are recognized in the aetiology of vascular dysfunction (Brook et al, 2002;D'Errico & Stapleton, 2019;Kampa & Castanas, 2008); however, PM 0.1 is of particular interest because these particles can elicit cardiovascular responses independent of any effects in the lung (for a review, see Riediker et al, 2019).…”

“…Indeed, studies show that both vaping and smoking produce endothelial dysfunction in humans, as evidenced by impaired flow‐mediated dilatation (Biondi‐Zoccai et al., 2019; Caporale et al., 2019; Carnevale et al., 2016; Chatterjee et al., 2021) and increases in pulse wave velocity (an index of arterial stiffness)(Franzen et al., 2018; Kerr et al., 2019; Vlachopoulos et al., 2016). In vivo animal models also show increased flow‐mediated dilatation (Rao et al., 2020), increased pulse wave velocity (Olfert et al ., 2018; Szostak et al., 2020) and impaired vascular reactivity with chronic Ecig and cigarette exposures (Burrage et al., 2021; Jin et al., 2021; Olfert et al, 2018). Thus, although it is too early to know whether Ecigs will produce the same long‐term outcomes for humans as smoking, based on evidence in the present study and existing literature, it seems unlikely to expect that Ecigs will be different/better for vascular health in humans than smoking.…”