Evidence mapPaperPMID 42375613Full record

ArticleFrontiers in pharmacology2026

Activation of BK channels ameliorates cardiac injury Via NFκB-NLRP3 signaling in angiotensin II-induced hypertension mouse model.

Long Zhao, Xingchen Wu, Xiaomao Luo, Anwen Zheng, Qiang Yue, Haidong Wang, Junko Ishida, Cesar A Romero, Douglas C Eaton, Janet D Klein and 3 more

Abstract read
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Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

13 authors.

Long ZhaoRenal Division, Department of Medicine, Emory University, Atlanta, GA, United States.
Xingchen WuRenal Division, Department of Medicine, Emory University, Atlanta, GA, United States.
Xiaomao LuoRenal Division, Department of Medicine, Emory University, Atlanta, GA, United States.
Anwen ZhengRenal Division, Department of Medicine, Emory University, Atlanta, GA, United States.
Qiang YueRenal Division, Department of Medicine, Emory University, Atlanta, GA, United States.
Haidong WangRenal Division, Department of Medicine, Emory University, Atlanta, GA, United States.
Junko IshidaRenal Division, Department of Medicine, Emory University, Atlanta, GA, United States.
Cesar A RomeroRenal Division, Department of Medicine, Emory University, Atlanta, GA, United States.
Douglas C EatonRenal Division, Department of Medicine, Emory University, Atlanta, GA, United States.
Janet D KleinRenal Division, Department of Medicine, Emory University, Atlanta, GA, United States.
Xiaonan H WangRenal Division, Department of Medicine, Emory University, Atlanta, GA, United States.
Yan XuDepartment of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Hui CaiRenal Division, Department of Medicine, Emory University, Atlanta, GA, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Hypertension-induced cardiac fibrosis leads to heart failure. Large-conductance calcium-activated potassium (BK) channels regulate vascular tone, and their activation may mitigate fibrosis. This study explores the impact of BK channel activation on angiotensin II (Ang II)-induced hypertension and cardiac fibrosis and its effects on nuclear factor-kappa B (NFκB) signaling. Methods: Male C57BL/6 J mice were infused with Ang II for 4 weeks to induce hypertension and cardiac fibrosis. The BK channel activator BMS-191011 was administered via intraperitoneal injection. Cardiac tissue was analyzed using histology, Western blotting and qPCR. Single channel recordings were used to analyze the activation of BKα channels. A dihydroethidium (DHE) Assay was used to detect superoxide (ROS) production. Superoxide Dismutase (SOD) was measured using a colorimetric activity kit. Results: The expression of BKα mRNA and protein abundance was decreased while markers of cardiac fibrosis (fibronectin, vimentin, αSMA and TGF-β) and ROS production were increased in the hearts of Ang II-induced hypertensive mice. In addition, macrophage infiltration was significantly increased along with inflammatory cytokines IFNγ, IL-6, IL-4, IL-10 and TNFα. The BK channel opener, BMS-191011, significantly reduced hypertension, cardiac fibrosis, and ROS production, but restored SOD in the hearts of Ang II-treated mice. In cultured macrophages, we found that Ang II increased inflammatory cytokines through NFκB-NLRP3-caspase-1 signaling. After Ang II treatment, BK channel activation inhibited NFκB, NLRP3 and caspase-1 expression. BK channel activation also suppressed NFκB-NLRP3 signaling, leading to reduced ROS accumulation and restored SOD activity. Conclusion: BK channel activation reduces Ang II-induced hypertension and cardiac fibrosis by modulating oxidative stress, inflammation and macrophage polarization through the NFκB-NLRP3 pathway. These findings implicate BK channel activators as a potential novel therapeutic strategy for hypertensive cardiomyopathy.

Indexed as

cardiac fibrosiscardiovascular diseasehypertrophyNFκBROSSOD

Identifiers

PMID42375613
PMCPMC13310761

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.