Histone Deacetylase Inhibitors Relax Mouse Aorta Partly through Their Inhibitory Action on L-Type Ca2+ Channels
Publication in refereed journal


摘要Histone deacetylase (HDAC) inhibitors modulate acetylation/deacetylation of histone and non-histone proteins. They have been widely used for cancer treatment. However, there are only a few reports investigating the effect of HDAC inhibitors on vascular tone regulation, most of which involves chronic treatment with HDAC inhibitors. In the present study, we found that two hydroxamate-based pan-HDAC inhibitors suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) could partially but acutely relax the high extracellular K+-induced contraction of mouse aortas. SAHA and TSA also attenuated the high extracellular K+-induced cytosolic Ca2+ rise, and inhibited L-type Ca2+ channel current in whole-cell patch clamp. These data demonstrated that SAHA could inhibit L-type Ca2+ channels to cause vascular relaxation. In addition, SAHA and TSA dose-dependently relaxed the arteries precontracted with phenylephrine. The relaxant effect of SAHA and TSA was greater in phenylephrine-precontracted arteries than in high K+-contracted arteries. While part of the relaxant effect of SAHA and TSA on phenylephrine-precontracted arteries was related to L-type Ca2+ channels, both agents could also induce relaxation via a mechanism independent of L-type Ca2+ channels. Taken together, HDAC inhibitors SAHA and TSA can acutely relax blood vessels via their inhibitory action on L-type Ca2+ channels and via another L-type Ca2+ channel-independent mechanism.
著者Changbo ZHENG, Mingkui ZHONG, Zenghua QI, Fan SHEN, Qiannan ZHAO, Lulu WU, Yu HUANG, Suk-
Ying TSANG, Xiaoqiang YAO
期刊名稱The Journal of Pharmacology and Experimental Therapeutics
頁次211 - 220

上次更新時間 2020-18-09 於 02:33