Adjuvant-induced arthritis promotes vascular hyporesponsiveness to phenylephrine through a nitric oxide-related mechanism

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-05-17 DOI:10.1590/1414-431X2024e13304

T.S. Araujo, M. A. Spadella, C.P. Carlos, C. R. Tirapelli, E.F.B. Chagas, J.C.D. Pinheiro, A.B. Chies

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Abstract

Arthritis has important cardiovascular repercussions. Phenylephrine-induced vasoconstriction is impaired in rat aortas in the early phase of the adjuvant-induced arthritis (AIA), around the 15th day post-induction. Therefore, the present study aimed to verify the effects of AIA on hyporesponsiveness to phenylephrine in rat aortas. AIA was induced by intradermal injection of Mycobacterium tuberculosis (3.8 mg/dL) in the right hind paw of male Wistar rats (n=27). Functional experiments in isolated aortas were carried out 15 days after AIA induction. Morphometric and stereological analyses of the aortas were also performed 36 days after the induction of AIA. AIA did not promote structural modifications in the aortas at any of the time points studied. AIA reduced phenylephrine-induced contraction in endothelium-intact aortas, but not in endothelium-denuded aortas. However, AIA did not change KCl-induced contraction in either endothelium-intact or denuded aortas. L-NAME (non-selective NOS inhibitor), 1400W (selective iNOS inhibitor), and ODQ (guanylyl cyclase inhibitor) reversed AIA-induced hyporesponsiveness to phenylephrine in intact aortas. 7-NI (selective nNOS inhibitor) increased the contraction induced by phenylephrine in aortas from AIA rats. In summary, the hyporesponsiveness to phenylephrine induced by AIA was endothelium-dependent and mediated by iNOS-derived NO through activation of the NO-guanylyl cyclase pathway.

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佐剂诱导的关节炎通过一氧化氮相关机制促进血管对苯肾上腺素的低反应性

关节炎对心血管有重要影响。在佐剂诱导的关节炎（AIA）早期，即诱导后第 15 天左右，苯肾上腺素诱导的大鼠主动脉血管收缩功能受损。因此，本研究旨在验证 AIA 对大鼠主动脉苯肾上腺素低反应性的影响。雄性 Wistar 大鼠（n=27）右后爪皮内注射结核分枝杆菌（3.8 mg/dL）诱导 AIA。在诱导 AIA 15 天后对离体主动脉进行功能实验。在诱导 AIA 36 天后，还对大动脉进行了形态计量学和立体学分析。在研究的任何时间点，AIA 都没有促进主动脉结构的改变。AIA 可减少内皮未受损的主动脉在苯肾上腺素诱导下的收缩，但不能减少内皮受损的主动脉在苯肾上腺素诱导下的收缩。然而，AIA 并没有改变内皮未受损或受损主动脉中 KCl 诱导的收缩。L-NAME（非选择性 NOS 抑制剂）、1400W（选择性 iNOS 抑制剂）和 ODQ（鸟苷酸环化酶抑制剂）逆转了 AIA 诱导的完整主动脉对苯肾上腺素的低反应性。7-NI（选择性 nNOS 抑制剂）增加了苯肾上腺素诱导的 AIA 大鼠主动脉收缩。总之，AIA 诱导的对苯肾上腺素的低反应性是内皮依赖性的，由 iNOS 通过激活 NO-guanylyl 环化酶途径衍生的 NO 介导。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.