Gender influence on the nitric oxide and endothelin expression in mesentery in a model of brain death in rats

• Grant number: 14/12968-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2014
• End date: August 31, 2015
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ana Cristina Breithaupt Faloppa
• Grantee: Guilherme Konishi Kudo
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The organ transplantation has evolved as the treatment of choice for many patients with end-stage disease. However, clinical studies show differences in the prognosis of short and long-term transplants due to donor gender. Clinical and experimental evidence also highlight the impact of brain death on the viability of the organ to be transplanted and show the importance of the donor state in the final results of the transplant. Brain death triggers the immune system activation which is characterized by the expression of inflammatory mediators to the organs. Although there is evidence that the immune response (innate and adaptive) differs between men and women, sexual dimorphism does not receive deserved attention as a potential factor for the different immune responses observed between men and women. Microcirculatory function is the main prerequisite for adequate tissue oxygenation and thus organ function, especially in sepsis or after organ transplantation. Several elements of the regulation of vascular tone, such as endothelin and nitric oxide are produced by the endothelial cells. The dysfunction of these cells is suggested as the trigger of ischemic-reperfusion. Postischemic interaction of neutrophils with the endothelium decreases capillary perfusion and thereby aggravates organ dysfunction. Sex hormones may exert modulatory role on the inflammatory response and contribute to the hemodynamic deterioration. Organic and immunological changes could favor the later appearance of the rejection phenomena in the recipient. Sex steroids can also exhibit direct effects on cells of the immune system. Preliminary results obtained with rats have indicated differences in cell mobilization after induction of brain death. From the idea that sexual dimorphism exists in the immune response to brain death and might be responsible for differences in the prognosis of organ transplants, in this study we aim to investigate the differences between the genders regarding the nitric oxide synthases and the endothelin expression in mesentery circulation in a model of brain death in rats.