Anti-inflammatory action of angiotensin-(1-7) on cardiovascular complications induced by experimental Sepsis

• Grant number: 21/05371-3
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Effective date (Start): March 01, 2022
• Effective date (End): May 31, 2025
• Field of knowledge: Health Sciences - Nursing - Medical-Surgical Nursing
• Principal Investigator: Luiz Guilherme de Siqueira Branco
• Grantee: Hadder Batista Silva
• Host Institution: Escola de Enfermagem de Ribeirão Preto (EERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 16/17681-9 - Pathophysiological changes during systemic inflammation, AP.TEM

Abstract

Recent studies have been shown an increased incidence of Cardiovascular Diseases (CVDs) in surviving patients of Sepsis and septic shock. Several inflammatory mediators have been considered to be responsible for this cardiovascular changes which can occurs between 1 and 5 years after the previous infection. The activation of the Renin Angiotensin System (RAS) and the increase of proinflammatory cytokines, Reactive Oxygen Species (ROS) and nitric oxide (NO) stand out. The synthesis of these inflammatory mediators can be modulated by substances such as angiotensin II (ANG II). During Sepsis, plasma concentrations of ANG II are increased, demonstrating the important contribution of RAS to the inflammatory process. Angiotensin-(1-7) [Ang- (1-7)], a biologically active angiotensinergic peptide, has been shown to mediate endocrine effects similar to ANG II. However, in contrast to ANG II, Ang-(1-7) exerts antioxidant and anti-inflammatory properties, decreasing RO, pro-inflammatory cytokines, iNOS expression and the CLP-induced NO concentration. Thus, Ang- (1-7) could act as an important cardioprotective pathway, mediated by the Mas receptor, in a CLP model. Therefore, the hypothesis of this project is that the intravenous administration of Ang- (1-7) can contribute to attenuating the cardiovascular dysfunction induced by experimental Sepsis in animals surviving CLP. (AU)