PDF(Pubmed)
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.
摘要：
关节炎具有重要的心血管影响。在佐剂诱导的关节炎（AIA）的早期阶段，去氧肾上腺素诱导的血管收缩在大鼠主动脉中受损，入职后第15天左右.因此,本研究旨在验证AIA对大鼠主动脉对去氧肾上腺素低反应性的影响。通过在雄性Wistar大鼠（n=27）的右后爪皮内注射结核分枝杆菌（3.8mg/dL）诱导AIA。在AIA诱导后15天,在分离的主动脉中进行功能实验。AIA诱导后36天，还进行了主动脉的形态测量和体视学分析。AIA在研究的任何时间点都不促进主动脉中的结构修饰。AIA降低了去氧肾上腺素诱导的内皮完整主动脉收缩，但不在内皮剥脱的主动脉中。然而,AIA在完整的内皮或裸露的主动脉中都没有改变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去氧肾上腺素的低反应性。7-NI（选择性nNOS抑制剂）增加了去氧肾上腺素在AIA大鼠主动脉中诱导的收缩。总之,AIA诱导的对去氧肾上腺素的低反应性是内皮依赖性的，并由iNOS衍生的NO通过激活NO-鸟苷酸环化酶途径介导。
