The Nitric Oxide-Donor Agent 3- (1,3-Dioxoisoindolin-2-Yl) Benzyl Nitrate Prevents Endothelial Dysfunction Induced By Angiotensin II In Isolated Aortic Rings From Rats.

The Nitric Oxide-Donor Agent 3- (1,3-Dioxoisoindolin-2-Yl) Benzyl Nitrate Prevents Endothelial Dysfunction Induced By Angiotensin II In Isolated Aortic Rings From Rats.

• Autor
• Barbara Terroni
• Co-autores
• Luis Henrique Oliveira de Moraes
• Resumo

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  Introduction: Sickle Cell Disease (SC) is a hereditary hemoglobinopathy, characterized by several cardiovascular damages, endothelial dysfunction (ED) and hypertension. Objective: To find out new drug candidates to treat SC symptoms, the molecular hybridization of thalidomide and hydroxyurea resulted in the discovery of the 3- (1,3-dioxoisoindolin-2-yl) benzyl nitrate (4C) with NO-donor properties. Methods: This work, was developed in the vascular vascular reactivity using aortic rings from male Wistar rats (200g/ 90 days). The project was approved by CEUA Nº 1295101219. First, it was analyzed the effective concentration induced by the 4C in the presence (E+) or absence of endothelium (E-) in order to characterize its effective participation in the vascular response. Moreover, it was evaluated the mechanism of action through measurement of the distinct components, the soluble guanylate cyclase pathway was inhibited by 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ), endothelial nitric oxide synthase (eNOS) by L-NG-Nitroarginine methyl ester(L-name), and hydroxocobalamin was used as nitric oxide (NO) scavenger. The ability of compound 4C to prevent ED angiotensin-induced after previous aortic rings incubation for 1 hour was studied. The aortic rings were divided into three groups: control (CT); angiotensin II (ANGII) and 4C plus ANGII. After incubation, vascular reactivity experiments were performed. The rings were precontracted; then, a dose-response curve with acetylcholine (ACH) was made. Analyzed using One-Way ANOVA followed by a Newman-Keuls post-test. Results: 4C demonstrated to be effective in promoting the vasodilation with (EMax E+:101.80 ± 3.33% n=9) and without (EMax E-: 111.80 ± 3.21%; n = 7). The Emax pathways: hydroxocobalamin (30.6±2.21%; n=10); ODQ (4.75±0.51%; n=10) and L-name (109±3.65; n=10) demonstrated that 4C has an independent L-name pathway. The ACH concentration-response curve compared pD2 among them: CT (6.73±0.1; n=7); ANG II (6.46± 0.04; n=9) and 4C (7.15±0.04; n=7). Conclusion: The compound 4C seems to be effective in preventing endothelial dysfunction and promotes vasodilation.

• Palavras-chave
• Nitric oxide donor; endothelial dysfunction; angiotensin II
• Modalidade
• Pôster
• Área Temática
• Disfunção endotelial