The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Trichostatin A Modulates Angiotensin II-induced Vasoconstriction and Blood Pressure Via Inhibition of p66shc Activation

  • Kang, Gun (Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University) ;
  • Lee, Yu Ran (Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University) ;
  • Joo, Hee Kyoung (Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University) ;
  • Park, Myoung Soo (Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University) ;
  • Kim, Cuk-Seong (Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University) ;
  • Choi, Sunga (Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University) ;
  • Jeon, ByeongHwa (Research Institute for Medical Sciences, Department of Physiology, School of Medicine, Chungnam National University)
  • Received : 2015.06.03
  • Accepted : 2015.07.01
  • Published : 2015.09.01
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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 ($AT_1R$) inhibitor, valsartan ($10{\mu}M$), but not by the $AT_2R$ inhibitor, PD123319. TSA ($1{\sim}10{\mu}M$) inhibited Ang II-induced p66shc phosphorylation in VSMCs and in HEK293T cells expressing $AT_1R$. Taken together, these results suggest that TSA treatment inhibited vasoconstriction and hypertension via inhibition of Ang II-induced phosphorylation of p66shc through $AT_1R$.

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References

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