Influence evaluation of the pravastatin antioxidant effects on the gelatinolytic activity of metalloproteinases 2 and 9 hypertensive pregnant rats

• Grant number: 20/01829-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): June 01, 2020
• Effective date (End): May 31, 2021
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Carlos Alan Candido Dias Junior
• Grantee: Cristal de Jesus Toghi
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Hypertensive disorders of pregnancy are the main causes of maternal and fetal mortality, characterized by elevations in maternal blood pressure which may compromise fetal development. The pathogenesis is still unknown, but there are theories that there is a decrease in the plasticity of the vessels of the maternal-fetal interface, placental ischemia accompanied by maternal endothelial dysfunction. Recently, it has been suggested that some endogenous mediators may be related and they seem to participate in the pathogenesis of gestational hypertension, namely: the decrease in the bioavailability of nitric oxide (NO) and the high activity of extracellular matrix metalloproteinases (MMPs). Therefore, this study aims to evaluate the impact of pravastatin on MMPs, since this statin has been shown to increase the bioavailability of NO and has provided antioxidant effects in hypertensive pregnant rats without affecting fetal development. To achieve this aim, pregnant rats will be divided into four groups: normotensive pregnant (Norm-Preg); pregnant rats treated with pravastatin (Preg + Prava); hypertensive pregnant rats (HTN-Preg) and hypertensive pregnant rats treated with pravastatin (HTN - Preg + Prava). Hypertension in pregnant rats will be induced by the DOCA-salt model, which consists of the administration of deoxycorticosterone acetate (DOCA) with concomitant replacement of drinking water by saline. The blood pressure of the rats and placentas and pups weights will be recorded, as well as gelatinolytic activity of MMP-2 and MMP-9, the metabolites of NO and redox balance will be examined. In addition, in order to assess the endothelial function of rats, we will perform the technique of vascular reactivity in the abdominal aorta. The hypothesis is that pravastatin, which has antioxidant actions, reduces the activity of MMPs elevated by gestational hypertension.