Demethoxycurcumin Preserves Renovascular Function by Downregulating COX-2 Expression in Hypertension.

Yingjuan Li,Liqun Ren,Danyang Tian,Chunhua Zhu

doi:10.1155/2016/9045736

Abstract

Hypertension-associated endothelial dysfunction is largely due to the exaggerated vasoconstrictor generation by cyclooxygenase-2 (COX-2). COX-2 is induced under inflammatory condition. Demethoxycurcumin (DMC) is a major component of Curcuma longa L, which possesses anti-inflammatory action. This study aimed to examine whether DMC protects endothelial function in hypertension by modulating COX-2. Changes in isometric tension showed that in vivo and ex vivo treatment with DMC rescued the attenuated endothelium-dependent relaxations (EDRs) and elevated endothelium-dependent contractions (EDCs) in the renal arteries of SHR, which were also corrected by acute usage of the COX-2 inhibitor celecoxib. The restoration of renovascular activity by DMC was accompanied by the normalization of COX-2 expression. The enhanced COX-2 expression observed in the renal arteries of hypertensive patients was suppressed by incubation of excised arteries with DMC for 12 hrs. In the renal arteries of Wistar-Kyoto rats (WKY), DMC prevented the endothelial dysfunction caused by angiotensin II. The reduction in the generation of nitric oxide (NO) and expression of eNOS phosphorylation (Ser1177) in human umbilical vein endothelial cells caused by angiotensin II (Ang II) were restored by DMC or celecoxib. Our findings suggest that DMC may decrease COX-2 expression and improve endothelial function in hypertension.

Highlights

Healthy endothelium is essential to maintain normal vascular tone by releasing vasodilators and vasoconstrictors [1, 2]
The aim of the present study was to test whether DMC protects renovascular function, and if so, whether COX-2 serves as a downstream effector
Blunted ACh-induced relaxation and pronounced ACh-induced contractions were observed in the renal arteries of the vehicle-treated spontaneous hypertensive rats (SHR) compared with the normotensive WistarKyoto rats (WKY) controls (Figures 1(b) and 1(c))

Summary

Introduction

Healthy endothelium is essential to maintain normal vascular tone by releasing vasodilators and vasoconstrictors [1, 2]. Endothelial dysfunction, owing to the imbalance between dilating and constricting factors, is often encountered in the common setting of cardiovascular risk factors such as hypertension [3]. Disturbed COX-2 metabolism contributes largely to the development of hypertension-associated endothelial dysfunction through overgeneration of vasoconstrictors [4]. A minimal amount of COX2 is expressed in the vascular wall. A striking upregulation of COX-2 is observed in the inflamed vascular tissue, which was documented extensively in hypertension [5]. Experimental and clinical findings have implicated the striking generation of COX-dependent endothelium-derived contracting factors in the initiation and development of endothelial dysfunction in hypertension. Vasoconstrictors and reactive oxygen species (ROS) produced by COX-2 result in disturbed endothelial dysfunction [6]

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Results