Histone Deacetylase Inhibitors Relax Mouse Aorta Partly through Their Inhibitory Action on L-Type Ca2+ Channels.
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Aorta
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Vasodilatación
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Canales de Calcio Tipo L
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Inhibidores de Histona Desacetilasas
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Ácidos Hidroxámicos
Límite:
Animals
Idioma:
En
Revista:
J Pharmacol Exp Ther
Año:
2017
Tipo del documento:
Article