Abstract
Gallic acid (GA) has been reported to have beneficial effects on cancer, vascular calcification, and diabetes-induced myocardial dysfunction. We hypothesized that GA controls hypertension via oxidative stress response regulation in an animal model for essential hypertension. Spontaneously hypertensive rats (SHRs) were administered GA for 16 weeks. GA treatment lowered elevated systolic blood pressure in SHRs through the inhibition of vascular contractility and components of the renin-angiotensin II system. In addition, GA administration reduced aortic wall thickness and body weight in SHRs. In SHRs, GA attenuated left ventricular hypertrophy and reduced the expression of cardiac-specific transcription factors. NADPH oxidase 2 (Nox2) and GATA4 mRNA expression was induced in SHR hearts and angiotensin II-treated H9c2 cells; this expression was downregulated by GA treatment. Nox2 promoter activity was increased by the synergistic action of GATA4 and Nkx2-5. GA seems to regulate oxidative stress by inhibiting the DNA binding activity of GATA4 in the rat Nox2 promoter. GA reduced the GATA4-induced Nox activity in SHRs and angiotensin II-treated H9c2 cells. GA administration reduced the elevation of malondialdehyde levels in heart tissue obtained from SHRs. These findings suggest that GA is a potential therapeutic agent for treating cardiac hypertrophy and oxidative stress in SHRs.
Highlights
Chronic hypertension adversely affects critical organs, such as brain, eyes, heart, and kidneys[1]
We investigated the effects of Gallic acid (GA) in SHR hearts by assessing left ventricular hypertrophy (LVH), oxidative stress-related gene expression, and reactive oxygen species (ROS) and NADPH oxidase (Nox) activity
We found that GATA4 and GATA6 mRNA levels were upregulated in SHRs, compared to WKY rats, and this upregulation was reduced by GA administration (Fig. 3A,B)
Summary
Chronic hypertension adversely affects critical organs, such as brain, eyes, heart, and kidneys[1]. Hypertension is the most important determinant for left ventricular hypertrophy (LVH) and is a major risk factor for cardiovascular diseases[2]. The activation of the renin-angiotensin-aldosterone system (RAAS), the production of vasoconstrictors, endothelial dysfunction, sodium intake, and oxidative stress play critical roles in hypertension[7]. The nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a membrane-bound enzyme. ROS have been reported to play an important role in the pathophysiology of hypertension[17]. The activities of Nox[1], Nox[2], and Nox[5] cause adverse effects, such as endothelial dysfunction, inflammation, and apoptosis, whereas Nox[4] plays a protective role in the vasculature[18]. Oxidative stress promotes endothelial dysfunction, inflammation, and vascular remodeling, as well as fibrosis, hypertrophy, and apoptosis[19,20,21]
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