Efeitos da Sepse Sobre o Envelhecimento Vascular

• Autor(a) principal: Pinto, Gustavo Costa
• Data de Publicação: 2021
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
• Texto Completo: http://repositorio.ufes.br/handle/10/14985
• topic: Sepse; envelhecimento; óxido nítrico; ciclooxigenase; reatividade vascular; disfunção vascular; subject.br-rjbn; Fisiologia

Sepsis is defined as organic dysfunction, caused by an unregulated host response to infection, which affects millions of people annually, and aging acts as an important risk factor for a worse prognosis and clinical outcome. Thus, the aim of our study was to evaluate the effects of sepsis on vascular reactivity in the context of aging in an experimental model of staphylococcal sepsis, 24 hours after its induction, in mice of the species Balb-c. Animals aged 3 and 12 months (3M and 12M respectively) were subjected to intraperitoneum incoculation of a 150 µL preparation with methicillinsensitive Staphylococcus Aureus (1.8 x 109 CFU/mL) for sepsis groups (SP) or phosphate buffer -saline (PBS) for the control groups (CT). Sespe increased lethality in both groups, being significantly higher in the 12M group, and increased plasma levels of circulating free DNA in a similar way. A reduction in vascular relaxation was observed in acetylcholine-dependent curves in both age groups, however, 12 M animals submitted to sepsis showed a reduction in vascular reactivity during phenylephrine-dependent curves, which was not observed in septic animals with 3M. Incubation with L-NAME, an inhibitor of the nitric oxide synthase (NOS) enzyme, reversed the hyporesponsiveness of the phenylephrine-dependent curves of animals with 12 M, the same was observed during the incubation with aminoguanidine, an inhibitor of the induced nitric oxide synthase enzyme (iNOS), suggesting the participation of iNOS-derived nitric oxide (NO) in the increase of the anti-contractile effect during sepsis. Incubation with indomethacin, a cyclooxygenase (COX) inhibitor, also reversed hyporesponsiveness in phenylephrine-dependent curves, strengthening the hypothesis of the presence of vasodilator prostanoids in reducing vascular reactivity to phenylephrine in 12 M animals. Furthermore, incubation with tempol, a superoxide dismutase (SOD) mimetic and losartan, an angiotensin 1 (AT1) receptor antagonist, further reduced the vasoconstrictor responses observed during the phenylephrine-dependent curves in 12 M animals, suggesting the presence of reactive oxygen species (ROS) and activity of the renin angiotensin aldosterone system (SRAA) in our study model. In conclusion, we observed that staphylococcal sepsis promotes vascular hyporesponsiveness to vasoconstrictor agents exclusively in aged animals by mechanisms that involve the production of iNOS-derived NO and vasodilator prostanoids from the COX pathway. These findings, added to the presence of ROS and RAAS products, may contribute to vascular failure and worse clinical outcome observed.