Cafeteria diet-induced obesity enhances the cardiac function and impairs the aortic contractility in mice that survived sepsis: the role of ERK1/2-eNOS-NO-sGC pathway

Cafeteria diet-induced obesity enhances the cardiac function and impairs the aortic contractility in mice that survived sepsis: the role of ERK1/2-eNOS-NO-sGC pathway

• Autor
• Natália Ferreira de Araújo
• Co-autores
• Daniela Esteves Ferreira dos Reis Costa , Natália Ribeiro Cabacinha Nóbrega , Naiara de Assis Rabelo Ribeiro , Alexandre Santos Bruno , Sérgio Ricardo Aluotto Scalzo Júnior , Stêfany Bruno de Assis Cau , Silvia Carolina Guatimosim Fonseca , Daniella Bonaventura
• Resumo

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  Introduction: The coexistence of obesity and sepsis has become frequent in clinical practice. However, the impact of obesity on the cardiovascular outcomes of sepsis remains unclear. Therefore, the aim of this study was to investigate how the cafeteria (CAF) diet-induced obesity influences the cardiovascular responses in mice that survived experimental sepsis. Methods: Male Balb/c mice (8 weeks old) were divided in four groups: (1) Control, (2) CLP, (3) CAF, and (4) CAF-CLP. The Control and CLP groups received a standard diet while the CAF and CAF-CLP groups received cafeteria diet for 30 days. On the 15th day of the diet, CLP and CAF-CLP groups were submitted to cecal ligation and puncture to sublethal sepsis induction, while Control and CAF groups were submitted only to cecal exposition. The Langendorff perfusion method, the measurement of cardiomyocyte contractility, and the vascular reactivity of the thoracic aorta were performed. Results: The isolated heart and cardiomyocytes of the CAF-CLP group showed a basal intrinsic function significantly increased in relation to those of the CLP group. However, when stimulated with increasing concentrations of isoprenaline, the heart responsiveness of the CAF-CLP group was significantly lower compared to the CLP group. Phenylephrine-induced vasoconstriction was significantly diminished in the CAF-CLP, which demonstrated hyporeactivity compared to the other groups. The CAF-CLP aortic hyporeactivity was completely restored by the endothelium mechanical removal. Moreover, PD98059, L-NAME or ODQ incubation partially reversed the CAF-CLP hyporeactivity, while LY,294-002, 1400W, 7-Ni, TEA, Catalase, or Captopril were not able to alter this vascular response. Conclusion: The CAF diet-induced obesity significantly alters the cardiovascular responses in mice that survived sepsis. In this way, the cardiovascular responses of the CAF-CLP group are characterized by increased cardiac function and impaired aortic contractility. This aortic hyporeactivity is essentially triggered by endothelial mediators among which the ERK1/2-eNOS-NO-sGC pathway is partially involved. 

   

   

• Palavras-chave
• obesity; sepsis; cardiac function; vascular hyporeactivity; nitric oxide
• Área Temática
• Apresentações Orais - Sessão IV

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