caa a22 4500 606235434 CHVBK 20210128101242.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s11010-015-2498-8 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2498-8 Maternal hypertension programs increased cerebral tissue damage following stroke in adult offspring [Elektronische Daten] [Nicole Ventura, Albert Jin, M. Tse, Nichole Peterson, R. Andrew, Jeffrey Mewburn, Stephen Pang] The maternal system is challenged with many physiological changes throughout pregnancy to prepare the body to meet the metabolic needs of the fetus and for delivery. Many pregnancies, however, are faced with pathological stressors or complications that significantly impact maternal health. A shift in this paradigm is now beginning to investigate the implication of pregnancy complications on the fetus and their continued influence on offspring disease risk into adulthood. In this investigation, we sought to determine whether maternal hypertension during pregnancy alters the cerebral response of adult offspring to acute ischemic stroke. Atrial natriuretic peptide gene-disrupted (ANP−/−) mothers exhibit chronic hypertension that escalates during pregnancy. Through comparison of heterozygote offspring born from either normotensive (ANP+/−WT) or hypertensive (ANP+/−KO) mothers, we have demonstrated that offspring exposed to maternal hypertension exhibit larger cerebral infarct volumes following middle cerebral artery occlusion. Observation of equal baseline cardiovascular measures, cerebrovascular structure, and cerebral blood volumes between heterozygote offspring suggests no added influences on offspring that would contribute to adverse cerebral response post-stroke. Cerebral mRNA expression of endothelin and nitric oxide synthase vasoactive systems demonstrated up-regulation of Et-1 and Nos3 in ANP+/−KO mice and thus an enhanced acute vascular response compared to ANP+/−WT counterparts. Gene expression of Na+/K+ ATPase channel isoforms, Atp1a1, Atp1a3, and Atp1b1, displayed no significant differences. These investigations are the first to demonstrate a fetal programming effect between maternal hypertension and adult offspring stroke outcome. Further mechanistic studies are required to complement epidemiological evidence of this phenomenon in the literature. Springer Science+Business Media New York, 2015 Stroke nationallicence Hypertension nationallicence Pregnancy nationallicence Fetal programming nationallicence Natriuretic peptide nationallicence Endothelin nationallicence Nitric oxide synthase nationallicence Na+/K+-ATPase nationallicence Ventura Nicole Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada aut Jin Albert Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada aut Tse M. Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada aut Peterson Nichole Department of Medicine (Neurology), Kingston General Hospital, Kingston, ON, Canada aut Andrew R. Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada aut Mewburn Jeffrey Cancer Research Institute Queen's University, Kingston, ON, Canada aut Pang Stephen Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 408/1-2(2015-10-01), 223-233 0300-8177 408:1-2<223 2015 408 11010 https://doi.org/10.1007/s11010-015-2498-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2498-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ventura Nicole Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada aut NATIONALLICENCE 700 1- Jin Albert Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada aut NATIONALLICENCE 700 1- Tse M. Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada aut NATIONALLICENCE 700 1- Peterson Nichole Department of Medicine (Neurology), Kingston General Hospital, Kingston, ON, Canada aut NATIONALLICENCE 700 1- Andrew R. Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada aut NATIONALLICENCE 700 1- Mewburn Jeffrey Cancer Research Institute Queen's University, Kingston, ON, Canada aut NATIONALLICENCE 700 1- Pang Stephen Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 408/1-2(2015-10-01), 223-233 0300-8177 408:1-2<223 2015 408 11010