Trichostatin A Modulates Angiotensin II-induced Vasoconstriction and Blood Pressure Via Inhibition of p66shc Activation

The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology
Gun KangByeong Hwa Jeon

Abstract

Histone deacetylase (HDAC) has been recognized as a potentially useful therapeutic target for cardiovascular disorders. However, the effect of the HDAC inhibitor, trichostatin A (TSA), on vasoreactivity and hypertension remains unknown. We performed aortic coarctation at the inter-renal level in rats in order to create a hypertensive rat model. Hypertension induced by abdominal aortic coarctation was significantly suppressed by chronic treatment with TSA (0.5 mg/kg/day for 7 days). Nicotinamide adenine dinucleotide phosphate-driven reactive oxygen species production was also reduced in the aortas of TSA-treated aortic coarctation rats. The vasoconstriction induced by angiotensin II (Ang II, 100 nM) was inhibited by TSA in both endothelium-intact and endothelium-denuded rat aortas, suggesting that TSA has mainly acted in vascular smooth muscle cells (VSMCs). In cultured rat aortic VSMCs, Ang II increased p66shc phosphorylation, which was inhibited by the Ang II receptor type I (AT1R) inhibitor, valsartan (10 µM), but not by the AT2R inhibitor, PD123319. TSA (1~10 µM) inhibited Ang II-induced p66shc phosphorylation in VSMCs and in HEK293T cells expressing AT1R. Taken together, these results suggest that TSA treatment inhibited va...Continue Reading

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Jul 18, 2012·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Sang Ki LeeByeong Hwa Jeon
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Citations

Sep 2, 2017·The Journal of Pharmacology and Experimental Therapeutics·Changbo ZhengXiaoqiang Yao
Jul 15, 2017·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Hee Kyoung JooByeong Hwa Jeon
Aug 11, 2020·BioMed Research International·Hanna JungGun Jik Kim
Sep 13, 2016·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Jian DuJunjie Qin
Jul 3, 2018·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Byeong Hyeok YeChi Dae Kim
Mar 19, 2016·British Journal of Pharmacology·Fabio Di LisaRainer Schulz
Sep 21, 2017·American Journal of Physiology. Endocrinology and Metabolism·Hae-Ahm LeeInkyeom Kim
Dec 8, 2020·Frontiers in Cell and Developmental Biology·Xiaona ChenHong Li

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Methods Mentioned

BETA
targeted mutation
transfection
fluorescence microscopy
histone acetylation
acetylation

Software Mentioned

Chartpro
ImageQuant

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