Evaluation of the pharmacological action of nebivolol and its repercussions in an in vitro model of preeclampsia

Abstract

Preeclampsia (PE) stands out as the main gestational hypertensive syndrome responsible for high rates of morbidity and mortality in Brazil and worldwide. The disease is characterized by hypertension (e140 / 90 mmHg), which in turn is often accompanied by proteinuria, in addition to dysfunction of target organs, such as kidneys and liver. The pathophysiology of PE is not yet fully elucidated, but it is known that placental ischemia and the release of vasoactive factors in the maternal blood stream play an important role in the development of major maternal endothelial dysfunction. The reduction of nitric oxide (NO) bioavailability is an extremely important factor for the harmful repercussions of the disease and can occur through the decoupling of the eNOS enzyme, which leads to a decrease in NO, and the synthesis, by the decoupled enzyme, of superoxide and consequently peroxynitrite, molecules that contribute to the generalized state of endothelial dysfunction. In this context, nebivolol appears as a potential treatment for the syndrome, since it is able to favor the dimerization of eNOS, decrease the synthesis of superoxide and consequently increase the bioavailability of NO. Therefore, in the present project, we aim to study the antioxidant effect of nebivolol in an in vitro model of PE, in addition to investigating, at the molecular level, what changes are promoted by the drug in endothelial cells incubated with PE plasma. Discoveries in this area may encourage the emergence of strategies that can be used both in the prevention and treatment of PE. (AU)