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Evaluation of the proton pump inhibitor effects on blood pressure, vascular function and nitric oxide bioavailability in gestational hypertension in rats

Abstract

Preeclampsia (PE) is a disease that occurs in pregnancy and is characterized by elevated maternal blood pressure accompanied by endothelial dysfunction. Its pathogenesis is still not well understood; however, placental ischemia and hypoxia has shown importance in pathophysiology. In PE there is an increase in oxidative stress, increases in antiangiogenic factors and decreases in vasodilator mediators, such as nitric oxide (NO). Studies show that proton pump inhibitors (PPIs) may compromise the bioavailability of NO in a pH-dependent manner and also reduce NO synthesis by inhibiting the activity of the enzyme DDAH (dimethylarginine dimethylaminohydrolase) that metabolizes ADMA (asymmetric dimethylarginine), which is an endogenous inhibitor of NO synthase (NOS). Thus, PPIs commonly used by pregnant women to relieve symptoms of gastric reflux may compromise the bioavailability of NO; however, these actions of PPIs are not elucidated in pregnancy as well as in gestational hypertension and PE. Therefore, in the present project we will use the experimental model of gestational hypertension and PE induced by RUPP, which consists of reduced uterine perfusion pressure and that has been shown to be very promising for mimicking pathophysiological responses found in human PE. Our main hypothesis is that the impairment of NO bioavailability caused by PPI will aggravate gestational hypertension. In addition, we will also evaluate markers of angiogenesis (sFlt-1, soluble fms-like tyrosine kinase-1) and PLGF (Placental Growth Factor) as well as DDHA and ADMA in this experimental model. This study evaluates the impact of the use of PPI on the bioavailability of NO in gestational hypertension experimentally induced. (AU)

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