KCa3.1 通道阻断剂 TRAM-34 和米诺环素可预防果糖诱发的大鼠高血压。

IF 3.2 3区 医学 Q2 PERIPHERAL VASCULAR DISEASE
Abdelrahman Hamad, Melike Hacer Ozkan
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引用次数: 0

摘要

背景:大鼠摄入高果糖会通过与小神经胶质细胞相关的神经炎症增加血压。由于中间传导钙激活钾通道(KCa3.1)能增强小胶质细胞的反应性,我们研究了使用 KCa3.1 通道阻断剂 TRAM-34 或米诺环素预处理是否能预防果糖喂养大鼠高血压的发生:研究对象是雄性 Wistar 大鼠,连续 21 天给它们喂食高果糖(在饮用水中含量为 10%)或自来水。果糖组还接受了 21 天的米诺环素或 TRAM-34 系统治疗。在 21 天结束时,我们测量了收缩压和舒张压(SBP 和 DBP)、用尾袖定期测量的心率(HR);通过 ELISA 测量了血浆中的促炎细胞因子和胰岛素水平,并通过 qPCR 测量了脊髓束核(NTS)中的神经炎症标记物。我们还检测了大鼠离体肠系膜动脉的内皮依赖性超极化(EDH)型血管舒张:结果:果糖组的 SBP、DBP 和 HR 均升高。米诺环素和 TRAM-34 均能显著阻止这些升高。果糖摄入还增加了血浆 IL-6、IL-1β、TNF-α 和胰岛素水平,而 TRAM-34 的预处理也阻止了这些增加。在果糖喂养的高血压大鼠的 NTS 样本中,Iba-1(而非 CD86)水平明显升高,这意味着小胶质细胞增殖。由内皮 KCa3.1 介导的 EDH 型血管舒张在果糖组中减弱;然而,TRAM-34 不会导致舒张进一步恶化:结论:TRAM-34 在预防果糖诱发的高血压方面与米诺环素一样有效,不会干扰 EDH 型血管舒张。此外,TRAM-34 还能缓解与高果糖相关的全身炎症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The KCa3.1 Channel Blocker TRAM-34 and Minocycline Prevent Fructose-Induced Hypertension in Rats.

Background: High fructose consumption increases blood pressure through microglia-related neuroinflammation in rats. Since intermediate-conductance calcium-activated potassium channels (KCa3.1) potentiates microglial reactivity, we examined whether the pretreatment with the KCa3.1 channel blocker TRAM-34 or minocycline prevents hypertension development in fructose-fed rats.

Methods: The study involved male Wistar rats that were given either high fructose (10% in drinking water) or tap water for 21 days. Fructose groups also received minocycline or TRAM-34 systemically for 21 days. We measured systolic and diastolic blood pressure (SBP and DBP), heart rate (HR) periodically with tail-cuff; proinflammatory cytokines, and insulin levels in plasma via Enzyme-linked immunosorbent assay (ELISA), and neuroinflammatory markers in the nucleus tractus solitarii (NTS) by qPCR at the end of 21 days. We also examined endothelium-dependent hyperpolarization (EDH)-type vasorelaxations in isolated mesenteric arteries of the rats ex vivo.

Results: SBP, DBP, and HR increased in the fructose group. Both minocycline and TRAM-34 significantly prevented these increases. Fructose intake also increased plasma interleukin-6, interleukin-1β, tumor necrosis factor-α, and insulin levels, whereas pretreatment with TRAM-34 prevented these increases as well. Iba-1, but not cluster of differentiation-86 levels were significantly higher in the NTS samples of fructose-fed hypertensive rats which implied microglial proliferation. EDH-type vasorelaxations mediated by endothelial KCa3.1 attenuated in the fructose group; however, TRAM-34 did not cause further deterioration in the relaxations.

Conclusions: TRAM-34 is as effective as minocycline in preventing fructose-induced hypertension without interfering with EDH-type vasodilation. Furthermore, TRAM-34 relieves high fructose-associated systemic inflammation.

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来源期刊
American Journal of Hypertension
American Journal of Hypertension 医学-外周血管病
CiteScore
6.90
自引率
6.20%
发文量
144
审稿时长
3-8 weeks
期刊介绍: The American Journal of Hypertension is a monthly, peer-reviewed journal that provides a forum for scientific inquiry of the highest standards in the field of hypertension and related cardiovascular disease. The journal publishes high-quality original research and review articles on basic sciences, molecular biology, clinical and experimental hypertension, cardiology, epidemiology, pediatric hypertension, endocrinology, neurophysiology, and nephrology.
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