Abstract: TH-PO0287
Activation of BK Channels Ameliorates Cardiac Injury in Angiotensin II-Induced Hypertension Mouse Model
Session Information
- Hypertension and CVD: Mechanisms
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1601 Hypertension and CVD: Basic
Authors
- Zhao, Long, Emory University School of Medicine, Atlanta, Georgia, United States
- Wu, Xingchen, Shanxi Agricultural University College of Animal Science and Veterinary Medicine, Taiyuan, Shanxi, China
- Luo, Xiaomao, Emory University School of Medicine, Atlanta, Georgia, United States
- Zheng, Anwen, Emory University School of Medicine, Atlanta, Georgia, United States
- Ishida, Junko, Kinjo Gakuin Daigaku Seikatsu Kankyo Gakubu, Nagoya, Aichi Prefecture, Japan
- Yue, Qiang, Emory University School of Medicine, Atlanta, Georgia, United States
- Eaton, Douglas C., Emory University School of Medicine, Atlanta, Georgia, United States
- Wang, Xiaonan H., Emory University School of Medicine, Atlanta, Georgia, United States
- Cai, Hui, Emory University School of Medicine, Atlanta, Georgia, United States
Background
Hypertension-induced cardiac fibrosis contributes to heart failure. Large-conductance calcium-activated potassium (BK) channels regulate vascular tone, and their activation may mitigate fibrosis. This study explores the role of BK channel activation on Angiotensin II (Ang II)-induced hypertensive cardiac fibrosis.
Methods
Male mice were subjected to Ang II infusion for four weeks to induce hypertension and cardiac fibrosis. The BK channel activator BMS-191011 was administered via i.p. Blood pressure (BP) was monitored by tail-cuff technique, and cardiac tissue was analyzed using histology, Western blotting and qPCR. Single channel recordings were used to analyze BK channel activity. Hydrogen peroxide (H2O2) was tested by Amplex Red Hydrogen Peroxide Kit. Dihydroethidium (DHE) Assay was used to detect superoxide. Superoxide Dismutase (SOD), a defense of oxidative enzyme, was measured using colorimetric activity kit. In vitro, Macrophages (RAW 264.7) were stimulated with Ang II, with or without BK activation to measure NFκB activation and macrophages polarization.
Results
The expression of BKα mRNA and protein abundance were decreased while cardiac fibrosis increased in the hearts of Ang II-induced hypertensive mice. Fibronectin, vimentin, and αSMA were significantly elevated in hearts of Ang II mice; conversely, BMS treatment attenuated the levels of these proteins. BK channel activation significantly reduced BP and cardiac fibrosis in Ang II-treated mice. Single-channel recordings confirmed increased BK channel activity induced by Ang II in HEK-BKα cells. The activation of BKα prevented Ang II-induced upregulation of inflammatory cytokines, such as TNFα, IL-1β, and TGFβ in the heart of Ang II mice. In addition, BK channel activation suppressed AhR-NFκB signaling, leading to reduced ROS accumulation, restored SOD activity. In macrophages, BK channel activation inhibited NLRP3 and caspase-1 expression, attenuated macrophage polarization toward M1 and M2 phenotypes induced by Ang II.
Conclusion
BK channel activation alleviates Ang II-induced hypertension and cardiac fibrosis by modulating oxidative stress, inflammation and macrophage polarization through AhR-NFκB pathway. These findings suggest BK channel activators as a promising therapeutic strategy for hypertension and cardiac fibrosis.
Funding
- Veterans Affairs Support