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抗氧化补充剂对高血压大鼠主动脉基础张力和血管重塑的不同影响。

Disparate Effect of Antioxidant Supplements on the Basal Tone and Vascular Remodeling of the Aorta in Hypertensive Rats.

机构信息

Instituto Superior de Investigaciones Biológicas (INSIBIO), CONICET-UNT, and Instituto de Fisiología, Facultad de Medicina, Universidad Nacional de Tucumán, San Miguel de Tucumán, Argentina.

Instituto Superior de Investigaciones Biológicas (INSIBIO), CONICET-UNT, and Instituto de Fisiología, Facultad de Medicina, Universidad Nacional de Tucumán, San Miguel de Tucumán, Argentina,

出版信息

J Vasc Res. 2020;57(5):261-275. doi: 10.1159/000507368. Epub 2020 Jun 18.

Abstract

BACKGROUND

Oxidative stress plays an essential role in the vascular tone in hypertension; however, the mechanisms remain unclear.

AIM

This study aimed to determine the antioxidant effect of tempol and vitamin C (Vit-C) on the basal tone and vascular remodeling of the aorta in nitric oxide (NO) deficiency-induced hypertensive rats.

METHOD

Male Sprague-Dawley rats were induced to hypertension by Nω-nitro-L-arginine methyl ester (L-NAME). Animals were randomized as follows: vehicle (Control: CR), CR-tempol, CR-Vit-C, L-NAME, L-NAME-tempol, and L-NAME-Vit-C. After 6 weeks of treatment, the basal aortic tone was evaluated by sodium nitroprusside (SNP) and calcium-free medium. Endothelial function, NO, reduced-to-oxidized glutathione (GSH/GSSG) ratio, resting membrane potential (mP), and vascular remodeling were also measured.

RESULTS

L-NAME rats showed an increased basal tone that was blunted by both SNP (-547 ± 69; n = 7 vs. CR: -7.5 ± 6.7 mg; n = 7; p < 0.001) and calcium-free medium. Tempol or Vit-C did not reverse hypertension, and the high basal tone was decreased only with tempol. In L-NAME rats, only tempol partially improved endothelial function, GSH-to-GSSG ratio, mP values, and vascular remodeling.

CONCLUSIONS

Tempol decreased calcium-dependent basal aortic tone and improved vascular homeostasis in L-NAME rats. Vit-C did not lead to a similar effect, suggesting that alterations in the superoxide dismutase pathway may play a role in the basal aortic tone.

摘要

背景

氧化应激在高血压的血管张力中起着重要作用;然而,其机制尚不清楚。

目的

本研究旨在确定替米泊芬(tempol)和维生素 C(Vit-C)对一氧化氮(NO)缺乏诱导的高血压大鼠主动脉基础张力和血管重构的抗氧化作用。

方法

雄性 Sprague-Dawley 大鼠通过 Nω-硝基-L-精氨酸甲酯(L-NAME)诱导高血压。动物随机分为以下几组:载体(对照:CR)、CR-tempol、CR-Vit-C、L-NAME、L-NAME-tempol 和 L-NAME-Vit-C。治疗 6 周后,通过硝普钠(SNP)和无钙介质评估主动脉基础张力。还测量了内皮功能、NO、还原型/氧化型谷胱甘肽(GSH/GSSG)比值、静息膜电位(mP)和血管重构。

结果

L-NAME 大鼠的基础张力增加,SNP(-547 ± 69;n = 7 与 CR:-7.5 ± 6.7 mg;n = 7;p < 0.001)和无钙介质均可使基础张力降低。替米泊芬或 Vit-C 均不能逆转高血压,仅替米泊芬可降低基础张力。在 L-NAME 大鼠中,只有替米泊芬部分改善了内皮功能、GSH/GSSG 比值、mP 值和血管重构。

结论

替米泊芬降低了钙依赖性主动脉基础张力,并改善了 L-NAME 大鼠的血管稳态。Vit-C 未产生类似效果,表明超氧化物歧化酶途径的改变可能在基础主动脉张力中起作用。

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