Edaravone inhibits pressure overload-induced cardiac fibrosis and dysfunction by reducing expression of angiotensin II AT1 receptor

Drug Design, Development and Therapy
Wei-Wei ZhangZhi-Qing Zhao

Abstract

Angiotensin II (Ang II) is known to be involved in the progression of ventricular dysfunction and heart failure by eliciting cardiac fibrosis. The purpose of this study was to demonstrate whether treatment with an antioxidant compound, edaravone, reduces cardiac fibrosis and improves ventricular function by inhibiting Ang II AT1 receptor. The study was conducted in a rat model of transverse aortic constriction (TAC). In control, rats were subjected to 8 weeks of TAC. In treated rats, edaravone (10 mg/kg/day) or Ang II AT1 receptor blocker, telmisartan (10 mg/kg/day) was administered by intraperitoneal injection or gastric gavage, respectively, during TAC. Relative to the animals with TAC, edaravone reduced myocardial malonaldehyde level and increased superoxide dismutase activity. Protein level of the AT1 receptor was reduced and the AT2 receptor was upregulated, as evidenced by the reduced ratio of AT1 over AT2 receptor (0.57±0.2 vs 3.16±0.39, p<0.05) and less locally expressed AT1 receptor in the myocardium. Furthermore, the protein level of angiotensin converting enzyme 2 was upregulated. In coincidence with these changes, edaravone significantly decreased the populations of macrophages and myofibroblasts in the myocardium, ...Continue Reading

Citations

Jun 3, 2020·Journal of Cellular and Molecular Medicine·Jae Gyun OhDongtak Jeong
Feb 27, 2020·International Journal of Hypertension·Yuejia DingJunping Zhang
Jul 10, 2019·Experimental and Therapeutic Medicine·Man ZhangDa-Qing Chen
Feb 8, 2020·Journal of Medicinal Chemistry·Lucienne Juillerat-Jeanneret
Mar 23, 2021·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Hisashi KaiAtsushi Katoh
Mar 11, 2019·ACS Biomaterials Science & Engineering·Zhoujiang ChenXiaohong Li
Sep 19, 2018·Free Radical Biology & Medicine·Ligia Akemi KiyunaJulio Cesar Batista Ferreira
Jul 4, 2018·Journal of Medicinal Chemistry·Lucienne Juillerat-JeanneretDela Golshayan

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Methods Mentioned

BETA
light microscopy
protein assay
electrophoresis
X-ray
MDA

Software Mentioned

SigmaPlot
Aperio ImageScope CS
ImageJ

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