Anti-atrial Fibrillatory Effects of the TRPC3 Channel Inhibitor Pyrazole-3 in Rats with Atrial Enlargement Induced by Chronic Volume Overload.

IF 1.7 4区医学 Q3 PHARMACOLOGY & PHARMACY

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI:10.1248/bpb.b25-00415

Megumi Aimoto, Yoshinobu Nagasawa, Taichi Kusakabe, Keisuke Kato, Akira Takahara

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Abstract

The effect of transient receptor potential canonical-3 (TRPC3) channel inhibitor pyrazole-3 (Pyr3) on the stability of atrial fibrillation (AF) was analyzed in a rat model of chronic volume overload. Male Wistar rats underwent aorto-venocaval shunt (AVS) surgery and received Pyr3 treatment intraperitoneally for 12 weeks. Morphological and electrophysiological assessments were performed at the end of the treatment period. Longer P-wave duration, atrial conduction time, and AF duration, in addition to greater atrial tissue weight, were detected in AVS rats compared with sham rats. Chronic Pyr3 administration prevented AVS-induced prolongation of P-wave duration and atrial conduction time, partially prevented atrial weight increase, and abbreviated AVS-induced prolongation of AF duration to similar levels as those in sham rats, without affecting the atrial effective refractory period. These results suggest that the TRPC3 inhibitor Pyr3 can ameliorate sustained AF associated with chronic volume overload by improving atrial conduction defects in AVS rats. Pharmacological inhibition of TRPC3 channels by Pyr3 thus represents a promising therapeutic strategy for preventing AF development related to structural modeling.

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TRPC3通道抑制剂吡唑-3对慢性容量负荷所致心房扩大大鼠的抗心房纤颤作用。

在慢性容量负荷大鼠模型中，分析瞬时受体电位-3 （TRPC3）通道抑制剂吡唑-3 （Pyr3）对心房颤动（AF）稳定性的影响。雄性Wistar大鼠行主动脉-静脉-腔静脉分流术（AVS），腹腔注射Pyr3治疗12周。在治疗期结束时进行形态学和电生理评估。与假手术大鼠相比，AVS大鼠p波持续时间、心房传导时间和房颤持续时间更长，心房组织重量更大。慢性给药Pyr3可阻止avs诱导的p波持续时间和心房传导时间延长，部分阻止心房重量增加，并将avs诱导的房颤持续时间延长缩短至与假手术大鼠相似的水平，但不影响心房有效不应期。这些结果表明，TRPC3抑制剂Pyr3可以通过改善AVS大鼠心房传导缺陷来改善慢性容量过载相关的持续性房颤。因此，Pyr3对TRPC3通道的药理抑制代表了一种有希望的治疗策略，可以预防与结构建模相关的房颤发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biological & pharmaceutical bulletin 医学-药学

CiteScore

3.50

自引率

5.00%

发文量

247

审稿时长

2 months

期刊介绍： Biological and Pharmaceutical Bulletin (Biol. Pharm. Bull.) began publication in 1978 as the Journal of Pharmacobio-Dynamics. It covers various biological topics in the pharmaceutical and health sciences. A fourth Society journal, the Journal of Health Science, was merged with Biol. Pharm. Bull. in 2012. The main aim of the Society’s journals is to advance the pharmaceutical sciences with research reports, information exchange, and high-quality discussion. The average review time for articles submitted to the journals is around one month for first decision. The complete texts of all of the Society’s journals can be freely accessed through J-STAGE. The Society’s editorial committee hopes that the content of its journals will be useful to your research, and also invites you to submit your own work to the journals.