Rosmarinic Acid Alleviates the Endothelial Dysfunction Induced by Hydrogen Peroxide in Rat Aortic Rings via Activation of AMPK

Hui Zhou,Bo Xu,Zhenhua Wang,Baocai Fu,Gang Li,Chengjun Ma,Jianxin Xie,Ji Li,Xiangquan Mi

doi:10.1155/2017/7091904

Abstract

Endothelial dysfunction is the key player in the development and progression of vascular events. Oxidative stress is involved in endothelial injury. Rosmarinic acid (RA) is a natural polyphenol with antioxidative, antiapoptotic, and anti-inflammatory properties. The present study investigates the protective effect of RA on endothelial dysfunction induced by hydrogen peroxide (H2O2). Compared with endothelium-denuded aortic rings, the endothelium significantly alleviated the decrease of vasoconstrictive reactivity to PE and KCl induced by H2O2. H2O2 pretreatment significantly injured the vasodilative reactivity to ACh in endothelium-intact aortic rings in a concentration-dependent manner. RA individual pretreatment had no obvious effect on the vasoconstrictive reaction to PE and KCl, while its cotreatment obviously mitigated the endothelium-dependent relaxation impairments and the oxidative stress induced by H2O2. The RA cotreatment reversed the downregulation of AMPK and eNOS phosphorylation induced by H2O2 in HAEC cells. The pretreatment with the inhibitors of AMPK (compound C) and eNOS (L-NAME) wiped off RA's beneficial effects. All these results demonstrated that RA attenuated the endothelial dysfunction induced by oxidative stress by activating the AMPK/eNOS pathway.

Highlights

The vascular endothelium plays critical roles in maintaining the vascular structure and function [1]
The 5.0 mM H2O2 pretreatment resulted in the significant decrease of the maximum contraction induced by PE or KCl in endothelium-denuded aortic rings (Figures 1(a) and 1(b)), which indicated that H2O2 induced more serious injury to the vascular smooth muscle in the endothelium-denuded aortic rings and the presence of the endothelium alleviated this injury
The oxidative burst derived from the neutrophil activation in the inflammation will produce more reactive oxygen species (ROS), there is no accurate concentration data of H2O2 reported

Summary

Introduction

The vascular endothelium plays critical roles in maintaining the vascular structure and function [1]. The endothelium releases both relaxing and contracting factors including nitric oxide (NO), prostacyclin, and endothelin, which contribute to the local regulation of vascular tone and the coagulation [2]. Whereas excess ROS will result in oxidative stress which contributes to vascular dysfunction in cardiovascular events [4], diabetes [5], stroke [6], atherosclerosis [7], and so forth, it is becoming increasingly clear that oxidative stress contributed to the development of the macrovascular complications [8]. Recent studies have shown that the mechanism of endothelial dysfunction is largely due to the reduced bioavailability of endothelium-derived NO by oxidative stress [9]. The presence of ROS reduces the bioavailability of NO [10] and results in the eNOS uncoupling which will result in more ROS formation [11]

Methods

Results

Conclusion