Hesperidin Prevents Nitric Oxide Deficiency-Induced Cardiovascular Remodeling in Rats via Suppressing TGF-β1 and MMPs Protein Expression.

Putcharawipa Maneesai,Parichat Prachaney,Veerapol Kukongviriyapan,Sarawoot Bunbupha,Thewarid Berkban,Prapassorn Potue,Poungrat Pakdeechote,Upa Kukongviriyapan

doi:10.3390/nu10101549

Putcharawipa Maneesai, Parichat Prachaney + Show 6 more

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https://doi.org/10.3390/nu10101549

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Journal: Nutrients	Publication Date: Oct 19, 2018
Citations: 38	License type: CC BY 4.0

Affiliation: Khon Kaen University, Mahasarakham University

Abstract

Hesperidin is a major flavonoid isolated from citrus fruits that exhibits several biological activities. This study aims to evaluate the effect of hesperidin on cardiovascular remodeling induced by n-nitro l-arginine methyl ester (l-NAME) in rats. Male Sprague-Dawley rats were treated with l-NAME (40 mg/kg), l-NAME plus hesperidin (15 mg/kg), hesperidin (30 mg/kg), or captopril (2.5 mg/kg) for five weeks (n = 8/group). Hesperidin or captopril significantly prevented the development of hypertension in l-NAME rats. l-NAME-induced cardiac remodeling, i.e., increases in wall thickness, cross-sectional area (CSA), and fibrosis in the left ventricular and vascular remodeling, i.e., increases in wall thickness, CSA, vascular smooth muscle cells, and collagen deposition in the aorta were attenuated by hesperidin or captopril. These were associated with reduced oxidative stress markers, tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta 1 (TGF-β1), and enhancing plasma nitric oxide metabolite (NOx) in l-NAME treated groups. Furthermore, up-regulation of tumor necrosis factor receptor type 1 (TNF-R1) and TGF- β1 protein expression and the overexpression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) was suppressed in l-NAME rats treated with hesperidin or captopril. These data suggested that hesperidin had cardioprotective effects in l-NAME hypertensive rats. The possible mechanism may involve antioxidant and anti-inflammatory effects.

Highlights

Nitric oxide (NO) is a crucial vasodilator derived from vascular endothelium to regulate vascular tone [1]
It is generally known that the main sequel of cardiovascular remodeling is heart failure, which is the major cause of death worldwide [6]
There were no significant differences in the systolic blood pressure of all the rats at the beginning of the study

Summary

Introduction

Nitric oxide (NO) is a crucial vasodilator derived from vascular endothelium to regulate vascular tone [1]. A reduction of NO production results in increased vascular resistance and high blood pressure. Nω -nitro L-arginine methyl ester (L-NAME), an L-arginine analogue, is widely used as an inhibitor of nitric oxide synthase (NOS) activity to represent an animal model of hypertension. It has been reported that L-NAME-induced hypertension in rats is characterized by insufficient. NO production, increased systemic oxidative stress, inflammation, and endothelial dysfunction [2]. L-NAME-induced hypertension and cardiovascular remodeling have been reported. The administration of L-NAME (40 mg/kg) for four or five weeks causes high blood pressure and cardiovascular remodeling, including left ventricular hypertrophy, myocardial fibrosis, and thickening of the vascular wall [3,4,5]. It is generally known that the main sequel of cardiovascular remodeling is heart failure, which is the major cause of death worldwide [6]

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