{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T18:03:52Z","timestamp":1757700232231,"version":"3.41.0"},"reference-count":39,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2016,9,24]],"date-time":"2016-09-24T00:00:00Z","timestamp":1474675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\"><jats:list-item><jats:p>Nitric oxide is essential in the vascular adaptation to pregnancy, as knockout mice lacking nitric oxide synthase (NOS3) have abnormal utero\u2010placental perfusion, hypertension and growth restriction.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>We previously showed with<jats:italic>ex vivo<\/jats:italic>studies on transgenic animals lacking NOS3 that adverse intrauterine environment alters fetal programming of vascular reactivity in adult offspring.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>The current research shows that altered vascular reactivity correlates with higher blood pressure<jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Our data suggest that higher blood pressure depends on both genetic background (NOS3 deficiency) and uterine environment, becomes more evident with age (&gt; 7 postnatal weeks), activity and stress, is gender specific (preponderant among males), and can be affected by the sleep\u2013awake cycle.<\/jats:p><\/jats:list-item><jats:list-item><jats:p><jats:italic>In utero<\/jats:italic>or early postnatal life (&lt; 7\u00a0weeks), before onset of hypertension, may represent a potential window for intervention to prevent future cardiovascular disorders.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Nitric oxide is involved in the vascular adaptation to pregnancy. Using transgenic animals, we previously showed that adverse intrauterine environment alters vascular reactivity in adult offspring. The aim of our study was to determine if altered vascular programming is associated with abnormal blood pressure (BP) profiles<jats:italic>in vivo<\/jats:italic>. Mice lacking a functional endothelial nitric oxide synthase (KO, NOS3<jats:sup>\u2212\/\u2212<\/jats:sup>) and wild\u2010type mice (WT, NOS3<jats:sup>+\/+<\/jats:sup>) were crossbred to generate homozygous NOS3<jats:sup>\u2212\/\u2212<\/jats:sup>(KO), maternally derived heterozygous NOS3<jats:sup>+\/\u2212<\/jats:sup>(KOM: mother with adverse intrauterine environment from NOS3 deficiency), paternally derived heterozygous NOS3<jats:sup>+\/\u2212<\/jats:sup>(KOP: mother with normal<jats:italic>in utero<\/jats:italic>milieu) and NOS3<jats:sup>+\/+<\/jats:sup>(WT) litters. BP was measured<jats:italic>in vivo<\/jats:italic>at 7, 14 and 21\u00a0weeks of age. After univariate analysis, multivariate population\u2010averaged linear regression models were used to identify factors affecting BP. When compared to WT offspring, systolic (SBP), diastolic (DBP) and mean (MAP) BP progressively increased from KOP, to KOM, and peaked among KO (<jats:italic>P<\/jats:italic>&lt;\u00a00.001), although significance was not reached for KOP. Higher BP was also associated with male gender, older age (&gt; 7 postnatal weeks), higher locomotor activity, daytime recordings, and recent blood pressure transducer insertion (<jats:italic>P<\/jats:italic>&lt;\u00a00.001). Post hoc analysis showed that KOM had higher SBP than KOP (<jats:italic>P<\/jats:italic>&lt;\u00a00.05). Our study indicates that adverse intrauterine environment contributes, along with multiple other factors, to account for hypertension; moreover,<jats:italic>in utero<\/jats:italic>or early postnatal life may represent a possible therapeutic window for prevention of cardiovascular disease later in life.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp272602","type":"journal-article","created":{"date-parts":[[2016,8,10]],"date-time":"2016-08-10T08:53:16Z","timestamp":1470819196000},"page":"7015-7025","source":"Crossref","is-referenced-by-count":10,"title":["Fetal programming of blood pressure in a transgenic mouse model of altered intrauterine environment"],"prefix":"10.1113","volume":"594","author":[{"given":"Giuseppe","family":"Chiossi","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Division of Maternal Fetal Medicine University of Texas Medical Branch Galveston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maged M.","family":"Costantine","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Division of Maternal Fetal Medicine University of Texas Medical Branch Galveston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"Tamayo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Division of Maternal Fetal Medicine University of Texas Medical Branch Galveston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary D. 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