Role of biliverdina on vasopressin release, inflammatory response and blood pressure in rats submitted to endotoxemia

• Grant number: 15/22289-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2016
• End date: November 30, 2016
• Field of knowledge: Health Sciences - Nursing
• Principal Investigator: Angelita Maria Stabile
• Grantee: Geyse Cristina Silva de Aguiar
• Host Institution: Escola de Enfermagem de Ribeirão Preto (EERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The sepsis or endotoxemia, in the case of the administration of bacterial fragments, is characterized by an exacerbated response of the immunological system to an infectious agent. That response leads to a production of pro and anti-inflammatory cytokines, as well as, the induction of enzymes, such as oxide nitric synthase (NOS) and the heme oxygenase (HO), culminating in fever, hypotension and multiple bankruptcy of the organs. The hypotension is one of the main reasons for the liberation of the vasopressin (AVP), which is a peptide hormone with vasoconstrictor action, however; during the hypotension induced by the sepsis, the plasmatic concentration of AVP is close to the basal values. Some studies suggest that nitric oxide (NO), a gas endogenously produced by NOS, which is responsible for the inhibiting the release of AVP during endotoxemia. The HO enzyme catalyzes the degradation of the heme molecule in three by-products, which are carbon monoxide (CO), iron (Fe) and biliverdin (BV). Especially BV is shown to have antioxidant actions that modulate the inflammatory response. Studies accomplished by our group demonstrated that the central administration of BV led to increased plasma concentrations of AVP during endotoxemia, however, the effect of peripheral administration of BV on the secretion of AVP has not been evaluated yet. Based on these data, the aim of this study is to evaluate whether the BV peripheral administration maintains the plasma concentration of high AVP, through inhibition of NO production and modulation of the production of pro-inflammatory cytokines in endotoxemic rats.