TNF-? Inhibition Blunted Renovascular Hypertension-Induced Endothelial Dysfunction

TNF-? Inhibition Blunted Renovascular Hypertension-Induced Endothelial Dysfunction

• Autor
• Thaís Ribeiro Vitorino
• Co-autores
• Bruno Mantovani , Gisele Fernanda Bonácio , Rose Inês Matos Batista , José Eduardo Tanus dos Santos , Elen Rizzi Sanchez
• Resumo

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  Introduction: Activation of the renin-angiotensin system is associated with vascular changes. Evidence suggests that the TNF-? is necessary for hypertrophy and cardiac fibrosis induced by angiotensin II (Ang II). Ang II and TNF-? can promote an increase in the formation of reactive oxygen species (ROS), which is the main factor responsible for the inhibition of nitric oxide (NO). The hypothesis of the present study is that chronic treatment with Etanercept (ETN; selective TNF-? inhibitor), decreases the ROS formation resulting in a greater bioavailability of NO in 2-kidney and 1-clip (2K1C) hypertensive animals. Methodology: Male Wistar rats (180-200g) Sham and 2K1C were treated with ETN (1 mg/Kg) or vehicle three times/week for 4 weeks. Systolic Blood Pressure (SBP) was assessed weekly. Endothelial dysfunction was performed by concentration-effect curves of acetylcholine (Ach) and sodium nitroprusside (SNP) aortic rings pre-contracted with phenylephrine. ROS in aortas was evaluated by a dihydroethidium (DHE) assay. The results were analyzed with two-factor ANOVA and Tukey test. Statistically different values were considered when p<0.05. Number Ethics Committee 15/2016. Results: SBP increased progressively in 2K1C animals, reaching 187±4 mmHg (p<0.05 vs. Sham) and treatment with ETN did not decrease SBP while maintaining 181±9 mmHg. 2K1C showed a reduction in relaxation induced by ACh (71±3%) when compared to the Sham (95±8%; p<0.05). ETN treatment restored impaired responses to Ach in 2K1C (p<0.05). No differences were observed in the SNP-induced relaxation curves in all groups, suggesting that vascular dysfunction is dependent on the endothelium. DHE oxidation was increased in 2K1C (194± 21%) when compared with Sham (92±11%), which was reversed by ETN treatment in 2K1C (91±24%). Conclusion: TNF-? inhibition did not decrease SBP in 2K1C but reversed endothelial dysfunction and ROS formation. Thus, ETN does not affect SBP but can reverse the change in target organs, such as vessels, for example.

• Palavras-chave
• TNF-?; Endothelial Dysfunction; Angiotensin
• Modalidade
• Pôster
• Área Temática
• Disfunção endotelial