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Histone Deacetylase Inhibitors Relax Mouse Aorta Partly through Their Inhibitory Action on L-Type Ca2+ Channels.
Zheng, Changbo; Zhong, Mingkui; Qi, Zenghua; Shen, Fan; Zhao, Qiannan; Wu, Lulu; Huang, Yu; Tsang, Suk-Ying; Yao, Xiaoqiang.
Afiliación
  • Zheng C; Department of Physiology, Anhui Medical University, Hefei, China (M.Z., F.S.); School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, China (C.Z.); and School of Biomedical Sciences and Li Ka Shing Institute of He
  • Zhong M; Department of Physiology, Anhui Medical University, Hefei, China (M.Z., F.S.); School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, China (C.Z.); and School of Biomedical Sciences and Li Ka Shing Institute of He
  • Qi Z; Department of Physiology, Anhui Medical University, Hefei, China (M.Z., F.S.); School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, China (C.Z.); and School of Biomedical Sciences and Li Ka Shing Institute of He
  • Shen F; Department of Physiology, Anhui Medical University, Hefei, China (M.Z., F.S.); School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, China (C.Z.); and School of Biomedical Sciences and Li Ka Shing Institute of He
  • Zhao Q; Department of Physiology, Anhui Medical University, Hefei, China (M.Z., F.S.); School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, China (C.Z.); and School of Biomedical Sciences and Li Ka Shing Institute of He
  • Wu L; Department of Physiology, Anhui Medical University, Hefei, China (M.Z., F.S.); School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, China (C.Z.); and School of Biomedical Sciences and Li Ka Shing Institute of He
  • Huang Y; Department of Physiology, Anhui Medical University, Hefei, China (M.Z., F.S.); School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, China (C.Z.); and School of Biomedical Sciences and Li Ka Shing Institute of He
  • Tsang SY; Department of Physiology, Anhui Medical University, Hefei, China (M.Z., F.S.); School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, China (C.Z.); and School of Biomedical Sciences and Li Ka Shing Institute of He
  • Yao X; Department of Physiology, Anhui Medical University, Hefei, China (M.Z., F.S.); School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, China (C.Z.); and School of Biomedical Sciences and Li Ka Shing Institute of He
J Pharmacol Exp Ther ; 363(2): 211-220, 2017 11.
Article en En | MEDLINE | ID: mdl-28860353
ABSTRACT
Histone deacetylase (HDAC) inhibitors modulate acetylation/deacetylation of histone and nonhistone proteins. They have been widely used for cancer treatment. However, there have been only a few studies investigating the effect of HDAC inhibitors on vascular tone regulation, most of which employed 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 high extracellular K+-contracted 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 demonstrate 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. Although 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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Aorta / Vasodilatación / Canales de Calcio Tipo L / Inhibidores de Histona Desacetilasas / Ácidos Hidroxámicos Límite: Animals Idioma: En Revista: J Pharmacol Exp Ther Año: 2017 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Aorta / Vasodilatación / Canales de Calcio Tipo L / Inhibidores de Histona Desacetilasas / Ácidos Hidroxámicos Límite: Animals Idioma: En Revista: J Pharmacol Exp Ther Año: 2017 Tipo del documento: Article