The Kv4 potassium channel modulator NS5806 attenuates cardiac hypertrophy in vivo and in vitro.

Autor: Cai Y; Department of Pharmacology, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, 050017, Hebei, China.; The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Province, Shijiazhuang, 050017, China.; The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, 050017, China.; Department of Pharmacy, Hebei General Hospital, Shijiazhuang, 050051, China.; Hebei Key Laboratory of Clinical Pharmacy, Shijiazhuang, 050051, China., Zhang J; Department of Pharmacology, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, 050017, Hebei, China.; The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Province, Shijiazhuang, 050017, China.; The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, 050017, China., Zhang H; Department of Pharmacology, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, 050017, Hebei, China.; The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Province, Shijiazhuang, 050017, China.; The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, 050017, China., Qi J; Department of Pharmacology, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, 050017, Hebei, China.; The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Province, Shijiazhuang, 050017, China.; The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, 050017, China., Shi C; Department of Pharmacology, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, 050017, Hebei, China.; The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Province, Shijiazhuang, 050017, China.; The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, 050017, China., Xu Y; Department of Pharmacology, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, 050017, Hebei, China. yanfangxu@hebmu.edu.cn.; The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Province, Shijiazhuang, 050017, China. yanfangxu@hebmu.edu.cn.; The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, 050017, China. yanfangxu@hebmu.edu.cn.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Aug 27; Vol. 14 (1), pp. 19839. Date of Electronic Publication: 2024 Aug 27.
DOI: 10.1038/s41598-024-70962-x
Abstrakt: The compound NS5806 is a Kv4 channel modulator. This study investigated the chronic effects of NS5806 on cardiac hypertrophy induced by transverse aortic constriction (TAC) in mice in vivo and on neonatal rat ventricular cardiomyocyte hypertrophy induced by endothelin-1 (ET-1) in vitro. Four weeks after TAC, NS5806 was administered by gavage for 4 weeks. Echocardiograms revealed pronounced left ventricular (LV) hypertrophy in TAC-treated mice compared with sham mice. NS5806 attenuated LV hypertrophy, as manifested by the restoration of LV wall thickness and weight and the reversal of contractile dysfunction in TAC-treated mice. NS5806 also blunted the TAC-induced increases in the expression of cardiac hypertrophic and fibrotic genes, including ANP, BNP and TGF-β. Electrophysiological recordings revealed a significant prolongation of action potential duration and QT intervals, accompanied by an increase in susceptibility to ventricular arrhythmias in mice with cardiac hypertrophy. However, NS5806 restored these alterations in electrical parameters and thus reduced the incidence of mouse sudden death. Furthermore, NS5806 abrogated the downregulation of the Kv4 protein in the hypertrophic myocardium but did not influence the reduction in Kv4 mRNA expression. In addition, NS5806 suppressed in vitro cardiomyocyte hypertrophy. The results provide novel insight for further ion channel modulator development as a potential treatment option for cardiac hypertrophy.
(© 2024. The Author(s).)
Databáze: MEDLINE
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