Placental nitric oxide formation and endothelium-dependent vasodilation underlie pravastatin effects against angiogenic imbalance, hypertension in pregnancy and intrauterine growth restriction

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Data

2019-04-01

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Chimini, Jessica Sabbatine [UNESP]
Possomato-Vieira, Jose Sergio [UNESP]
da Silva, Maria Luiza Santos [UNESP]
Dias-Junior, Carlos A. [UNESP]

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Resumo

Pre-eclampsia and hypertensive disorders of pregnancy are frequently associated with foeto-placental growth restriction, and that may be triggered by angiogenic imbalance and endothelial dysfunction. Impaired nitric oxide (NO) 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, NO involvement in pravastatin effects during maternal hypertension and foeto-placental development is unclear. Therefore, we aimed to examine pravastatin effects on placental NO formation, endothelium-dependent vasodilation, systolic blood pressure and foeto-placental 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-Preg), pregnancy+pravastatin (Preg-Prava), hypertensive pregnancy (HTN-Preg) and hypertensive pregnancy+pravastatin (HTN-Preg+Prava). Our results showed that pravastatin treatment blunts hypertension and foeto-placental growth restriction. Also, increases in placental NO levels were found in the HTN-Preg+Prava group. Pravastatin prevents impaired endothelium-dependent acetylcholine-induced vasodilation, exacerbated contractile response to phenylephrine and increases in oxidative stress in the HTN-Preg+Prava group. Increased soluble fms-like tyrosine kinase-1-to-placental growth factor (sFlt-1/PlGF) ratio is reversed by pravastatin treatment in the HTN-Preg+Prava group. We conclude that NO formation and endothelium-dependent vasodilation underlie pleiotropic effects associated with pravastatin treatment against hypertension in pregnancy, intrauterine growth restriction, vascular dysfunction and angiogenic imbalance.

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hypertensive pregnancy, nitric oxide, rats, statins, vascular reactivity

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Basic and Clinical Pharmacology and Toxicology, v. 124, n. 4, p. 385-393, 2019.