Maternal electronic cigarette use during pregnancy affects long-term arterial function in offspring

Abstract

Vaping, or electronic cigarette (ecig) use, is prevalent among pregnant women, although little is known about the effects of perinatal ecig use on cardiovascular health of the progeny (even when using nicotine-free e-liquid). Maternal toxicant inhalation may adversely affect vital conduit vessel development. We tested the hypothesis that perinatal exposure to maternal vaping would lead to a dose-dependent dysfunction that would persist into later life of offspring. Pregnant Sprague-Dawley rats were exposed to either nicotine-free (ecig0) or nicotine-containing ecig aerosol (18 mg/mL, ecig18) starting on gestational day 2 and continued until pups were weaned (postnatal day 21). Pups were never directly exposed. Conduit artery function (stiffness and reactivity) and structure were assessed in 3- and 7-mo-old offspring. At 3 mo, pulse wave velocity (PWV) in the ecig0 and ecig18 offspring was significantly higher than controls in both the 20 puffs/day (6.6 ± 2.1 and 4.8 ± 1.3 vs. 3.2 ± 0.7 m/s, respectively, P < 0.05, means ± SD) and in 60 puffs/day exposure cohort (7.5 ± 2.8 and 7.5 ± 2.5 vs. 3.2 ± 0.5 m/s, respectively, P < 0.01). Wire myography revealed (range of 23%-31%) impaired aortic relaxation in all ecig exposure groups (with or without nicotine). Incubation of vessels with TEMPOL or Febuxostat reversed the aortic dysfunction, implicating the involvement of reactive oxygen species. Nearly identical changes and pattern was seen in vascular outcomes of 7-mo-old offspring. The take-home message from this preclinical study is that maternal vaping during pregnancy, with or without nicotine, leads to maladaptations in vascular (aortic) development that persist into adult life of offspring.NEW & NOTEWORTHY We observe a significant alteration in arterial structure and function in adolescent and adult offspring due to developmental exposure to toxicants resulting from perinatal maternal vaping. Taken together with previous work that described lasting dysfunction in cerebral microvasculature in offspring, these data underscore the adverse consequences of maternal exposure to electronic cigarette aerosol in conduit and resistance vessels alike, irrespective of nicotine content.

Keywords: aorta; arterial stiffness; in utero; vaping; vascular reactivity.

Graphical abstract

Figure 1.

In vivo arterial stiffness data [measured as pulse wave velocity (PWV)] using Doppler microultrasound of left common carotid artery in (isoflurane) anesthetized offspring at 3 and 7 mo of age. Offspring only received in utero exposure from maternal vaping with (18 mg/mL) or without (0 mg) nicotine (ecig18 and ecig0, respectively). n = 10–14/offspring for 3 mo; N = 3–5/group for 7 mo. All data shown are means ± SE. *P < 0.05, ***P < 0.001, ****P < 0.0001 vs. controls. ecig, electronic cigarette.

Figure 2.

Representative photomicrographs (scale bar = 1 mm) of abdominal aorta stained with (A) Verhoeff–Van Gieson for elastin fibers (purple-black) and (B) Masson’s Trichrome for collagen fibers (blue) showing decreased elastin and increased collagen content in aorta offspring with history of maternal exposed to e-cigarette containing 18 mg/mL or 0 mg nicotine (ecig18 and ecig0, respectively) during pregnancy. Controls are offspring with maternal exposure to ambient air. C: density quantification from respective elastin and collagen images (panel 1) from 3- (left) and 7-mo-old (right) offspring (expressed relative % to whole aorta area) and the ratio of elastin/collagen (panel 2). Data are means ± SE. N = 8 rats per group for 3 mo, N = 6 rats per group for 7 mo old. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 vs. controls. ecig, electronic cigarette.

Figure 3.

Ex vivo wire myography data showing relaxation responses of preconstricted thoracic aortic segments to increasing concentrations of methacholine (MCh) in offspring at 3 (A and B) and 7 mo (C and D) of age. Maternal exposure occurred with e-cigarettes with nicotine (ecig18 = 18 mg/mL) or without nicotine (ecig0 = 0 mg/mL). Controls are offspring with maternal exposure to ambient air. B and D: the maximal MCh dose (i.e., 10⁻⁵ M) from 3- and 7-mo-old offspring, respectively. All data are means ± SE. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 vs. controls. ecig, electronic cigarette.

Figure 4.

Ex vivo wire myography data showing thoracic aorta maximal responses in 3 (A and C) or 7 mo old (B and D) to either sodium nitroprusside (SNP, an endothelium-independent nitric oxide donor; A and B) or U46619 (U46, a vasoconstrictor; C and D). All responses are shown as a percentage of maximal KCl constriction. ecig, electronic cigarette.

Figure 5.

Data showing effect on the maximal methacholine dose (Mch 10⁻⁵M) responses (previously shown in Fig. 3) when treated with 1) nitric oxide inhibitor (l-NAME), 2) superoxide dismutase mimetic (TEMPOL), and 3) xanthine oxidase (XO)-specific inhibitor Febuxostat. Thoracic aorta are from 3- and 7-mo-old offspring who were only exposed in utero from maternal exposure to e-cigarette aerosol with (18 mg/mL) or without (0 mg) nicotine (ecig18 and ecig0, respectively). Controls are offspring with maternal exposure to ambient air. All data shown are means ± SE. ***P < 0.0001. ecig, electronic cigarette.