{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:39:45Z","timestamp":1772159985843,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,1,4]],"date-time":"2018-01-04T00:00:00Z","timestamp":1515024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006741","name":"Stiftelsen Frimurare Barnhuset i Stockholm","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006741","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005969","name":"Universit\u00e0 di Bologna","doi-asserted-by":"publisher","award":["RFO 2013\u20102015"],"award-info":[{"award-number":["RFO 2013\u20102015"]}],"id":[{"id":"10.13039\/501100005969","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Paediatrica"],"published-print":{"date-parts":[[2018,4]]},"abstract":"Abstract<\/jats:title>\n \n Aim<\/jats:title>\n Gather \u2018proof\u2010of\u2010concept\u2019 evidence of the adverse developmental potential of cotinine (a seemingly benign biomarker of recent nicotine\/tobacco smoke exposure).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Pregnant C57 mice drank nicotine\u2010 or cotinine\u2010laced water for 6 wks from conception (\n \n N\n PRE<\/jats:sub>\n <\/jats:styled-content>\n = 2% saccharin + 100\n \u03bc<\/jats:italic>\n g nicotine\/mL;\n \n C\n PRE<\/jats:sub>\n <\/jats:styled-content>\n = 2% saccharin + 10\n \u03bc<\/jats:italic>\n g cotinine\/mL) or 3 wks after birth (\n \n C\n POST<\/jats:sub>\n <\/jats:styled-content>\n = 2% saccharin + 30\n \u03bc<\/jats:italic>\n g cotinine\/mL). Controls drank 2% saccharin (\n CTRL<\/jats:styled-content>\n ). At 17 \u00b1 1 weeks (male pups;\n CTRL<\/jats:styled-content>\n n = 6;\n \n C\n POST<\/jats:sub>\n <\/jats:styled-content>\n n = 6;\n \n C\n PRE<\/jats:sub>\n <\/jats:styled-content>\n n = 8;\n \n N\n PRE<\/jats:sub>\n <\/jats:styled-content>\n n = 9), we assessed (i) cardiovascular control during sleep; (ii) arterial reactivity\n ex vivo<\/jats:italic>\n ; and (iii) expression of genes involved in arterial constriction\/dilation.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Blood cotinine levels recapitulated those of passive smoker mothers\u2019 infants. Pups exposed to cotinine exhibited (i) mild bradycardia \u2013 hypotension at rest (p < 0.001); (ii) attenuated (\n \n C\n PRE<\/jats:sub>\n <\/jats:styled-content>\n , p < 0.0001) or reverse (\n \n C\n POST<\/jats:sub>\n <\/jats:styled-content>\n ; p < 0.0001)\n BP<\/jats:styled-content>\n stress reactivity; (iii) adrenergic hypocontractility (p < 0.0003), low protein kinase C (p < 0.001) and elevated adrenergic receptor\n mRNA<\/jats:styled-content>\n (p < 0.05; all drug\u2010treated arteries); and (iv) endothelial dysfunction (\n \n N\n PRE<\/jats:sub>\n <\/jats:styled-content>\n only).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Cotinine has subtle, enduring developmental consequences. Some cardiovascular effects of nicotine can plausibly arise via conversion into cotinine. Low\u2010level exposure to this metabolite may pose unrecognised perinatal risks. Adults must avoid inadvertently exposing a foetus or infant to cotinine as well as nicotine.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/apa.14181","type":"journal-article","created":{"date-parts":[[2017,12,9]],"date-time":"2017-12-09T20:22:52Z","timestamp":1512850972000},"page":"638-646","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Long\u2010term cardiovascular reprogramming by short\u2010term perinatal exposure to nicotine's main metabolite cotinine"],"prefix":"10.1111","volume":"107","author":[{"given":"Stefano","family":"Bastianini","sequence":"first","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences (PRISM Lab) Alma Mater Studiorum Universit\u00e0 di Bologna Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viviana","family":"Lo Martire","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences (PRISM Lab) Alma Mater Studiorum Universit\u00e0 di Bologna Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Silvani","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences (PRISM Lab) Alma Mater Studiorum Universit\u00e0 di Bologna Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna","family":"Zoccoli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences (PRISM Lab) Alma Mater Studiorum Universit\u00e0 di Bologna Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Berteotti","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences (PRISM Lab) Alma Mater Studiorum Universit\u00e0 di Bologna Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugo","family":"Lagercrantz","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health Neonatal Unit Karolinska Institutet Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"Arner","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology (Genetic Physiology) Karolinska Institutet Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9677-2870","authenticated-orcid":false,"given":"Gary","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health Neonatal Unit Karolinska Institutet Stockholm Sweden"},{"name":"Centre for Sleep Health and Research Sleep Investigation Laboratory Royal North Shore Hospital Sydney Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,1,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/apa.12538"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(97)80001-9"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1983.222"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.99107s2349"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64859-6"},{"key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S0022-3565(25)26365-0","article-title":"Studies on the respiratory and cardiovascular effects of (\u2212)\u2010cotinine","volume":"137","author":"Borzelleca JF","year":"1962","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199403000-00015"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.114.219881"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3109\/14767050902994515"},{"key":"e_1_2_11_11_1","volume-title":"WHO recommendations for the prevention and management of tobacco use and second\u2010hand smoke exposure in pregnancy","author":"World Health Organization","year":"2013"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1109582"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep41698"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.192463599"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-8206.1999.tb00350.x"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2004.05.009"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12989-014-0035-7"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.80.5.1309"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.2000.6004"},{"key":"e_1_2_11_20_1","first-page":"923","article-title":"Blood pressure in smokers and non\u2010smokers: epidemiologic findings","volume":"8","author":"Green M","year":"1986","journal-title":"Am Heart J"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.81.7.850"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409782102"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00477.2009"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000155325.41507.e0"},{"key":"e_1_2_11_25_1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/S0022-3565(25)24766-8","article-title":"Protein kinase C and vascular smooth muscle contractility: effects of inhibitors and down\u2010regulation","volume":"257","author":"Merkel LA","year":"1991","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-007-0176-4"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-011-1432-7"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.239145"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.229641"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.142695"},{"key":"e_1_2_11_31_1","volume-title":"Easter, 1916. the collected poems of W. B. Yeats","author":"Yeats WB","year":"1994"}],"container-title":["Acta Paediatrica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fapa.14181","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apa.14181","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T09:11:08Z","timestamp":1751101868000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apa.14181"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,4]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1111\/apa.14181"],"URL":"https:\/\/doi.org\/10.1111\/apa.14181","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/193003","asserted-by":"object"}]},"ISSN":["0803-5253","1651-2227"],"issn-type":[{"value":"0803-5253","type":"print"},{"value":"1651-2227","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,4]]},"assertion":[{"value":"2017-09-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-12-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}