Inhibition of Extracellular Signal-Regulated Kinases Ameliorates Hypertension-Induced Renal Vascular Remodeling in Rat Models

Li Jing,Fengying Guo,Ping Andy Li,Jianzhong Zhang,Xin An,Kan Yang,Jinping Sun

doi:10.3390/ijms12128333

Abstract

The aim of this study is to investigate the effect of the extracellular signal-regulated kinases 1/2 (ERK1/2) inhibitor, PD98059, on high blood pressure and related vascular changes. Blood pressure was recorded, thicknesses of renal small artery walls were measured and ERK1/2 immunoreactivity and erk2 mRNA in renal vascular smooth muscle cells (VSMCs) and endothelial cells were detected by immunohistochemistry and in situ hybridization in normotensive wistar kyoto (WKY) rats, spontaneously hypertensive rats (SHR) and PD98059-treated SHR. Compared with normo-tensive WKY rats, SHR developed hypertension at 8 weeks of age, thickened renal small artery wall and asymmetric arrangement of VSMCs at 16 and 24 weeks of age. Phospho-ERK1/2 immunoreactivity and erk2 mRNA expression levels were increased in VSMCs and endothelial cells of the renal small arteries in the SHR. Treating SHR with PD98059 reduced the spontaneous hypertension-induced vascular wall thickening. This effect was associated with suppressions of erk2 mRNA expression and ERK1/2 phosphorylation in VSMCs and endothelial cells of the renal small arteries. It is concluded that inhibition of ERK1/2 ameliorates hypertension induced vascular remodeling in renal small arteries.

Highlights

Elevated arterial blood pressure is known to induce vascular structural change, which is termed as vascular remodeling (VR)
The results revealed that while inhibition of extracellular signal-regulated kinases 1/2 (ERK1/2) ameliorated the progression of VR, it failed to reduce blood pressure of spontaneously hypertensive rats (SHR)
Our results showed that spontaneous hypertension increased the thickness of renal small artery wall and the proliferation of vascular smooth muscle cells (VSMCs)

Summary

Introduction

Elevated arterial blood pressure is known to induce vascular structural change, which is termed as vascular remodeling (VR). Previous studies have suggested that VR is a pathophysiological basis for the progression of hypertension and for the development of other cardiovascular diseases [1]. Multiple factors, including blood pressure, oxidative stress, extracellular matrix and vascular smooth muscle cells (VSMCs) influence VR [2]. Modulating these factors could reduce or even reverse VR, thereby suppressing the progression of hypertension. Angiotensin-converting enzyme inhibitor (ACEI) has been shown to reduce blood pressure and to reverse the cardiovascular remodeling [3]

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