{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T15:47:12Z","timestamp":1762876032564},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,11,15]],"date-time":"2018-11-15T00:00:00Z","timestamp":1542240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pre\u2010eclampsia and hypertensive disorders of pregnancy are frequently associated with foeto\u2010placental growth restriction, and that may be triggered by angiogenic imbalance and endothelial dysfunction. Impaired nitric oxide (<jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>) bioavailability seems to be involved in these pathophysiological changes observed in hypertensive pregnancy. Pravastatin has shown efficacy and to be safe during hypertension in pregnancy. However, <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> involvement in pravastatin effects during maternal hypertension and foeto\u2010placental development is unclear. Therefore, we aimed to examine pravastatin effects on placental <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> formation, endothelium\u2010dependent vasodilation, systolic blood pressure and foeto\u2010placental development in hypertensive pregnant rats. Biochemical determinants of angiogenesis and oxidative stress were also assessed. Pregnant rats were distributed into four groups: normal pregnancy (Norm\u2010Preg), pregnancy+pravastatin (Preg\u2010Prava), hypertensive pregnancy (<jats:styled-content style=\"fixed-case\">HTN<\/jats:styled-content>\u2010Preg) and hypertensive pregnancy+pravastatin (<jats:styled-content style=\"fixed-case\">HTN<\/jats:styled-content>\u2010Preg+Prava). Our results showed that pravastatin treatment blunts hypertension and foeto\u2010placental growth restriction. Also, increases in placental <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> levels were found in the <jats:styled-content style=\"fixed-case\">HTN<\/jats:styled-content>\u2010Preg+Prava group. Pravastatin prevents impaired endothelium\u2010dependent acetylcholine\u2010induced vasodilation, exacerbated contractile response to phenylephrine and increases in oxidative stress in the <jats:styled-content style=\"fixed-case\">HTN<\/jats:styled-content>\u2010Preg+Prava group. Increased soluble fms\u2010like tyrosine kinase\u20101\u2010to\u2010placental growth factor (<jats:styled-content style=\"fixed-case\">sF<\/jats:styled-content>lt\u20101\/Pl<jats:styled-content style=\"fixed-case\">GF<\/jats:styled-content>) ratio is reversed by pravastatin treatment in the <jats:styled-content style=\"fixed-case\">HTN<\/jats:styled-content>\u2010Preg+Prava group. We conclude that <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> formation and endothelium\u2010dependent vasodilation underlie pleiotropic effects associated with pravastatin treatment against hypertension in pregnancy, intrauterine growth restriction, vascular dysfunction and angiogenic imbalance.<\/jats:p>","DOI":"10.1111\/bcpt.13149","type":"journal-article","created":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T03:38:21Z","timestamp":1539574701000},"page":"385-393","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Placental nitric oxide formation and endothelium\u2010dependent vasodilation underlie pravastatin effects against angiogenic imbalance, hypertension in pregnancy and intrauterine growth restriction"],"prefix":"10.1111","volume":"124","author":[{"given":"Jessica Sabbatine","family":"Chimini","sequence":"first","affiliation":[{"name":"Department of Pharmacology Biosciences 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