Perivascular adipose tissue contributes to lethal sepsis-induced vasoplegia in rats

Autor(es)

Awata, Wanessa M. C. ^{[1, 2]} ; Gonzaga, Natalia A. ^{[1, 2]} ; Borges, Vanessa F. ^[1] ; Silva, Carla B. P. ^[3] ; Tanus-Santos, Jose E. ^[1] ; Cunha, Fernando Q. ^[1] ; Tirapelli, Carlos R. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Programa Posgrad Farmacol, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Escola Enfermagem Ribeirao Preto, DEPCH, Lab Farmacol, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Programa Posgrad Toxicol, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Pharmacology; v. 863, NOV 15 2019.
• Citações Web of Science: 0

Resumo

It is well established that sepsis induces vascular hyporesponsiveness to vasoconstrictors. Perivascular adipose tissue (PVAT) displays anti-contractile action in various blood vessels. We hypothesized that sepsis would increase the anti-contractile effect of PVAT aggravating sepsis-induced vasoplegia. Male Wistar Hannover rats were subjected to lethal sepsis by cecal ligation and puncture (CLP) method. Aorta or PVAT were collected for functional or biochemical assays 6 h after CLP surgery. Functional experiments showed that sepsis increased the anti-contractile action of PVAT in both endothelium-intact and endothelium-denuded aortas. Carboxy-PTIO, L-NAME and ODQ reversed the hypocontractility mediated by PVAT in aortas from septic rats. Inhibition of nNOS and iNOS with 7-nitroindazole and 1400 W attenuated PVAT-mediated hypocontractility during sepsis. Similar results were found in the presence of indomethacin and Ro1138452, a selective prostacyclin IP receptor antagonist. However, neither tiron nor catalase affected phenylephrine-induced contraction in aortas from septic rats. Increased levels of superoxide anion (O-2(center dot-)) and 6-keto-prostaglandin F-1 alpha, (stable product of prostacyclin) were detected in PVAT from septic rats. In situ quantification of reactive oxygen species and nitric oxide (NO) using fluorescent dyes revealed increased levels of both in PVAT from septic rats. The novelty of our study is that PVAT contributes to sepsis-induced vasoplegia by releasing NO and prostacyclin. These findings suggested that signaling pathways in PVAT may be considered as potential novel pharmacological therapeutic targets during sepsis-induced vasoplegia. (AU)

• Processo FAPESP: 17/24123-5 - Impacto do consumo crônico de etanol sobre os danos cardíacos e vasculares induzidos pela sepse experimental: avaliação da participação da iNOS
• Beneficiário: Carlos Renato Tirapelli
• Modalidade de apoio: Auxílio à Pesquisa - Regular