{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T04:54:59Z","timestamp":1781499299973,"version":"3.54.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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 (NF\u03baB) signaling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male C57BL\/6\u00a0J mice were infused with Ang II for 4\u00a0weeks 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 BK\u03b1 channels. A dihydroethidium (DHE) Assay was used to detect superoxide (ROS) production. Superoxide Dismutase (SOD) was measured using a colorimetric activity kit.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , macrophages (RAW 264.7) were stimulated with Ang II, to detect NF\u03baB activation and macrophage polarization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The expression of BK\u03b1 mRNA and protein abundance was decreased while markers of cardiac fibrosis (fibronectin, vimentin, \u03b1SMA and TGF-\u03b2) 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 IFN\u03b3, IL-6, IL-4, IL-10 and TNF\u03b1. 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 NF\u03baB-NLRP3-caspase-1 signaling. After Ang II treatment, BK channel activation inhibited NF\u03baB, NLRP3 and caspase-1 expression. BK channel activation also suppressed NF\u03baB-NLRP3 signaling, leading to reduced ROS accumulation and restored SOD activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>BK channel activation reduces Ang II-induced hypertension and cardiac fibrosis by modulating oxidative stress, inflammation and macrophage polarization through the NF\u03baB-NLRP3 pathway. These findings implicate BK channel activators as a potential novel therapeutic strategy for hypertensive cardiomyopathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1739677","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T04:28:00Z","timestamp":1781497680000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Activation of BK channels ameliorates cardiac injury Via NF\u03baB-NLRP3 signaling in angiotensin II-induced hypertension mouse model"],"prefix":"10.3389","volume":"17","author":[{"given":"Long","family":"Zhao","sequence":"first","affiliation":[{"name":"Renal Division, Department of Medicine, Emory University","place":["Atlanta, GA, United States"]},{"name":"Department of Nephrology, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingchen","family":"Wu","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Emory University","place":["Atlanta, GA, United States"]},{"name":"College of Veterinary Medicine, Shanxi Agricultural University","place":["Taigu, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomao","family":"Luo","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Emory University","place":["Atlanta, GA, United States"]},{"name":"College of Veterinary Medicine, Shanxi Agricultural University","place":["Taigu, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Emory University","place":["Atlanta, GA, United States"]},{"name":"Emory College of Arts and Sciences, Emory University","place":["Atlanta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Yue","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Emory University","place":["Atlanta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haidong","family":"Wang","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Emory University","place":["Atlanta, GA, United States"]},{"name":"College of Veterinary Medicine, Shanxi Agricultural University","place":["Taigu, Shanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Ishida","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Emory University","place":["Atlanta, GA, United States"]},{"name":"Department of Food and Nutritional Environment, College of Human Life and Environment, Kinjo Gakuin University","place":["Nagoya, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar A.","family":"Romero","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Emory University","place":["Atlanta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas C.","family":"Eaton","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Emory University","place":["Atlanta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet D.","family":"Klein","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Emory University","place":["Atlanta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan H.","family":"Wang","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Emory University","place":["Atlanta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Cai","sequence":"additional","affiliation":[{"name":"Renal Division, Department of Medicine, Emory University","place":["Atlanta, GA, United States"]},{"name":"Nephrology Section, Atlanta VA Medical Center","place":["Decatur, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1111\/cei.12467","article-title":"Angiotensin II in inflammation, immunity and rheumatoid arthritis","volume":"179","author":"Chang","year":"2015","journal-title":"Clin. 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