Long-term cardiovascular re-programming by short-term perinatal exposure to nicotine's main metabolite cotinine.
Acta Paediatr. 2017 Dec 09;:
Authors: Bastianini S, Martire VL, Silvani A, Zoccoli G, Berteotti C, Lagercrantz H, Arner A, Cohen G
AIM: Gather "proof-of-concept" evidence of the adverse developmental potential of cotinine (a seemingly benign biomarker of recent nicotine / tobacco smoke exposure).
METHODS: Pregnant C57 mice drank nicotine or cotinine-laced water for 6wks from conception (NPRE = 2% saccharin+100μg nicotine/ml; CPRE = 2% saccharin + 10μg cotinine/ml) or 3wks after birth (CPOST = 2% saccharin + 30μg cotinine/ml). Controls drank 2% saccharin (CTRL). At 17±1weeks (male pups; CTRL n=6; CPOST n=6; CPRE n=8; NPRE n=9) we assessed (i) cardiovascular control during sleep; (ii) arterial reactivity ex vivo; (iii) expression of genes involved in arterial constriction / dilation.
RESULTS: Blood cotinine levels recapitulated those of passive smoker mothers-infants. Pups exposed to cotinine exhibited (i) mild bradycardia - hypotension at rest (p<0.001); (ii) attenuated (CPRE , p<0.0001) or reverse (CPOST ; p<0.0001) BP stress reactivity; (iii) adrenergic hypo-contractility (p<0.0003), low Protein Kinase C (p<0.001) and elevated adrenergic receptor mRNA (p<0.05; all drug-treated arteries); (iv) endothelial dysfunction (NPRE only).
CONCLUSION: Cotinine has subtle, enduring developmental consequences. Some cardiovascular effects of nicotine can plausibly arise via conversion to cotinine. Low-level exposure to this metabolite may pose unrecognized perinatal risks. Adults must avoid inadvertently exposing a fetus or infant to cotinine as well as nicotine. This article is protected by copyright. All rights reserved.
PMID: 29224235 [PubMed - as supplied by publisher]