Tetramethylpyrazine Protects against Hydrogen Peroxide-Provoked Endothelial Dysfunction in Isolated Rat Aortic Rings: Implications for Antioxidant Therapy of Vascular Diseases.

Xiaojia Ni,Chi Wai Lau,Xiaogeng Shi,Chi Ming Wong,Siu Ling Wong,Yefeng Cai,Yu Huang

doi:10.1155/2014/627181

Abstract

Background and Objectives. Oxidative stress can initiate endothelial dysfunction and atherosclerosis. This study evaluated whether tetramethylpyrazine (TMP), the predominant active ingredient in Rhizoma Ligustici Wallichii (chuanxiong), prevents endothelial dysfunction in a rat model of oxidative stress. Methods. Isolated rat aortic rings were pretreated with various drugs before the induction of endothelial dysfunction by hydrogen peroxide (H2O2). Changes in isometric tension were then measured in acetylcholine- (ACh-) relaxed rings. Endothelial nitric oxide synthase (eNOS) expression was evaluated in the rings by Western blotting, and superoxide anion (O2 ∙−) content was assessed in primary rat aortic endothelial cells by dihydroethidium- (DHE-) mediated fluorescence microscopy. Results. ACh-induced endothelium-dependent relaxation (EDR) was disrupted by H2O2 in endothelium-intact aortic rings. H2O2-impaired relaxation was ameliorated by acute pretreatment with low concentrations of TMP, as well as by pretreatment with catalase and the NADPH oxidase inhibitors, apocynin and diphenyleneiodonium (DPI). TMP, apocynin, and DPI also reduced O2 ∙− accumulation in endothelial cells,but TMP failed to alter eNOS expression in aortic rings incubated with H2O2. Conclusions. TMP safeguards against oxidative stress-induced endothelial dysfunction, suggesting that the agent might find therapeutic utility in the management of vascular diseases. However, TMP's role in inhibiting NADPH oxidase and its vascular-protective mechanism of action requires further investigation.

Highlights

Excessive production of reactive oxygen species (ROS) by vascular endothelial cells contributes to endothelial dysfunction [1] which initiates atherosclerosis [2]
Phe (0.3 μM) was utilized to provoke contraction in aortic rings isolated from adult Sprague Dawley rats, while ACh was employed to induce endothelium-dependent relaxation (EDR) in the Phe-contracted rings
ACh-induced EDR was markedly impaired in the rat aortic rings after 60 min exposure to H2O2 (200 μM) (Table 1, Figure 1)

Summary

Introduction

Excessive production of reactive oxygen species (ROS) by vascular endothelial cells contributes to endothelial dysfunction [1] which initiates atherosclerosis [2]. Additional efforts are directed toward interrupting ongoing oxidative processes in the vessel wall so as to prevent ROS-provoked endothelial impairment [7]. In this regard, antioxidants, which directly remove ROS threats, are emerging as one of the more promising treatments for vascular diseases in the recent years [8]. Oxidative stress can initiate endothelial dysfunction and atherosclerosis. This study evaluated whether tetramethylpyrazine (TMP), the predominant active ingredient in Rhizoma Ligustici Wallichii (chuanxiong), prevents endothelial dysfunction in a rat model of oxidative stress. TMP safeguards against oxidative stress-induced endothelial dysfunction, suggesting that the agent might find therapeutic utility in the management of vascular diseases. TMP’s role in inhibiting NADPH oxidase and its vascular-protective mechanism of action requires further investigation

Methods

Results

Discussion

Conclusion