Effects of Angiotensin-(1-7) and Angiotensin II on Acetylcholine-Induced Vascular Relaxation in Spontaneously Hypertensive Rats.

Feng Zhang,Changlei Bao,Yu Xu,Haiyang Tang,Peng Li,Ying Han,Yan Pan,Shuo Sun,Aidong Chen,Jian Wang

doi:10.1155/2019/6512485

Abstract

Endothelial dysfunction of small arteries occurs in patients with hypertension and in various hypertensive models. Endothelial function is usually evaluated by the degree of acetylcholine- (ACh-) induced vascular relaxation. Our previous study has found that compared to Wistar-Kyoto rats (WKY), ACh-induced vasodilatation was attenuated significantly in the mesenteric artery (MA), coronary artery (CA), and pulmonary artery (PA) of spontaneously hypertensive rats (SHR). This study investigated the influence of angiotensin- (Ang-) (1-7) and Ang II on blood pressure and ACh-induced vascular relaxation, as well as their interactive roles and downstream signal pathways in SHR and WKY. Intravenous injection of Ang II significantly increased, while Ang-(1-7) decreased the mean arterial pressure (MAP) in SHR. Ang-(1-7) improved ACh-induced relaxation in the MA, CA, and PA of SHR, while Ang II further attenuated it, which were inhibited by pretreatment with Mas receptor antagonist A-779 or AT1 receptor antagonist losartan, respectively. Ang-(1-7) decreased the basal arterial tension, and Ang II induced great vasoconstriction in SHR. Pretreatment with Ang-(1-7) inhibited the Ang II-induced pressor response, vasoconstriction, and the effects on ACh-induced relaxation in SHR. AT1 receptor expression was higher, while nitric oxide (NO), cGMP, and protein kinase G (PKG) levels of arteries were lower in SHR than in WKY. Ang II decreased, while Ang-(1-7) increased, the levels of NO, cGMP, and PKG of arteries. In addition, pretreatment with Ang-(1-7) inhibited the Ang II-induced reduction of NO, cGMP, and PKG in SHR. These results indicate that the activation of the Mas receptor by Ang-(1-7) can improve endothelial function and decrease MAP in SHR and inhibit the deteriorative effect of Ang II on endothelial function through the NO-cGMP-PKG pathway.

Highlights

The integrity of vascular endothelial function plays an important role in maintaining equilibrium and homeostasis of vascular tension in a normal physiological state [1]
As we had talked about in a previous study [15], the mesenteric artery (MA), coronary artery (CA), and pulmonary artery (PA) have been shown to play a major role in the damaging effects of hypertension; we continue choosing these particular vessels for this study to investigate the effects of Ang (1-7) and Ang II on endothelial function
The present study demonstrates the following new findings: (1) Ang-(1-7) decreased blood pressure, while Ang II elevated it; (2) Ang-(1-7) enhanced ACh-induced vascular relaxation, while Ang II further attenuated it in the MA, CA, and PA of spontaneously hypertensive rats (SHR)

Summary

Introduction

The integrity of vascular endothelial function plays an important role in maintaining equilibrium and homeostasis of vascular tension in a normal physiological state [1]. Acetylcholine (ACh) stimulates endothelial cells to release NO and induce vasodilatation; ACh-induced vasodilatation is usually used to evaluate endothelial function [1, 4] Some factors, such as hypoxia, increased oxidative stress, increased inflammatory factors, and vascular mechanical dystonia, hurt artery endothelial cells and cause endothelial dysfunction [5]. Impaired NO release caused by endothelial dysfunction of small arteries and subsequent impaired vascular relaxation are implicated in the development and progression of hypertension [13] and involved in the further progression of organ damage in hypertension [14]. We used the MA, CA, and PA to determine the effects of Ang-(1-7) and Ang II on ACh-induced arterial relaxation, the influence of Ang-(1-7) on Ang II-induced responses, and their signal molecular mechanisms in SHR and WKY

Materials and Methods

Results

Discussion