血管功能障碍和纤维化在中风倾向的自发性高血压大鼠:醛固酮 – 盐皮质激素受体 – NOX1轴

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所属分类:疗效
摘要

我们质疑醛固酮和氧化应激是否在重度高血压血管损伤起到一定的作用,并研究了这个NOX1的作用…

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血管功能障碍和纤维化在中风倾向的自发性高血压大鼠:醛固酮 - 盐皮质激素受体 -  NOX1轴

摘要

宗旨

我们质疑醛固酮和氧化应激。在严重的高血压血管损伤起到一定的作用,并研究NOX1在这一过程中的作用。

材料和方法

我们研究了肠系膜动脉,主动脉和从WKY血管平滑肌细胞(VSMC)和SHRSP大鼠。的依普利酮或canrenoic酸(CA)(盐皮质激素受体(MR)阻滞剂),ML171(NOX1抑制剂)和EHT1864(Rac1的/ 2抑制剂)进行了评估血管作用。 NOX1基因敲除小鼠进行了研究。容器和血管平滑肌细胞中探查​​Noxs,活性氧(ROS)和促纤维化/炎症信号。

主要发现

醛固酮和半乳凝素-3的血压和血浆水平增加在SHRSP与WKY。乙酰胆碱诱导的血管舒张降低(61%对115%)和苯肾上腺素诱导的收缩在SHRSP与WKY(的Emax增加132.8%和96.9%,,P < 0.05). Eplerenone, ML171 and EHT1864 attenuated hypercontractility in SHRSP. Vascular expression of collagen, fibronectin, TGFβ, MCP-1, RANTES, MMP2, MMP9 and p66Shc was increased in SHRSP versus WKY. These changes were associated with increased ROS generation, 3-nitrotyrosine expression and Nox1 upregulation. Activation of vascular p66Shc and increased expression of Nox1 and collagen I were prevented by CA in SHRSP. Nox1 expression was increased in aldosterone-stimulated WKY VSMCs, an effect that was amplified in SHRSP VSMCs (5.2vs9.9 fold-increase). ML171 prevented aldosterone-induced VSMC Nox1-ROS production. Aldosterone increased vascular expression of fibronectin and PAI-1 in wild-type mice but not in Nox1-knockout mice.

的意义

[123 ]我们的研究结果表明,醛固酮,其在SHRSP增加,诱导通过MR-NOX1-p66Shc介导的过程的血管损伤调节促纤维化和促炎症信号传导途径。

关键词

氧化stressVascular remodelingVascular functionSignal transductionHypertensionMineralocorticoid receptorsView摘要

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