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These factors contribute to excessive oxidative stress, adverse cardiac remodeling, and dysregulation of the nitric oxide\u2010soluble guanylate cyclase\u2010cyclic guanosine monophosphate (NO\u2010sGC\u2010cGMP) signaling pathway. Given the urgent need for effective treatments, this study investigated the potential of sGC stimulators to mitigate HF progression. We utilized male hypertensive Ren\u20102 transgenic (TGR) rats and a volume\u2010overload HF model induced by an aortocaval fistula (ACF). Rats received the sGC stimulator BAY 41\u20138543 (3\u2009mg\/kg\/day) for 30\u2009weeks, while normotensive Hannover Sprague\u2013Dawley rats served as controls. At the study endpoint (40\u2009weeks of age), left ventricular tissue was analyzed using mass spectrometry, Western blotting, and histological assessment. TGR rats treated with sGC stimulators exhibited a significant increase in key antioxidant proteins (SOD1, CH10, ACSF2, NDUS1, DHE3, GSTM2, and PCCA), suggesting enhanced resistance to oxidative stress. However, sGC stimulator treatment also upregulated extracellular matrix remodeling markers (MMP\u20102, TGF\u2010\u03b2, and SMAD2\/3), which are typically associated with fibrosis. Despite this, Masson's trichrome staining revealed reduced collagen deposition in both TGR and TGR\u2010ACF rats receiving sGC stimulators. Notably, all untreated TGR\u2010ACF rats succumbed before the study endpoint, preventing direct assessment of sGC stimulator effects in advanced HF. These findings highlight the therapeutic potential of sGC stimulators in HF, particularly through their antioxidant effects. However, their concurrent influence on fibrosis warrants further investigation to optimize treatment strategies.<\/jats:p>","DOI":"10.1002\/prp2.70087","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T23:24:46Z","timestamp":1743463486000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Soluble Guanylate Cyclase Stimulator, BAY41\u20108543: A Promising Approach for the Treatment of Chronic Heart Failure Caused by Pressure and Volume Overload"],"prefix":"10.1002","volume":"13","author":[{"given":"Adriana","family":"Marti\u0161kov\u00e1","sequence":"first","affiliation":[{"name":"Centre of Experimental Medicine Slovak Academy of Sciences, Institute for Heart Research  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0438-3956","authenticated-orcid":false,"given":"Mat\u00fa\u0161","family":"S\u00fdkora","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine Slovak Academy of Sciences, Institute for Heart Research  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1592-0072","authenticated-orcid":false,"given":"Nat\u00e1lia","family":"Andelov\u00e1","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine Slovak Academy of Sciences, Institute for Heart Research  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miroslav","family":"Ferko","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine Slovak Academy of Sciences, Institute for Heart Research  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Gawrys","sequence":"additional","affiliation":[{"name":"Centre for Experimental Medicine Institute for Clinical and Experimental Medicine  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katar\u00edna","family":"Andelov\u00e1","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine Slovak Academy of Sciences, Institute for Heart Research  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Kala","sequence":"additional","affiliation":[{"name":"Centre for Experimental Medicine Institute for Clinical and Experimental Medicine  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lud\u011bk","family":"\u010cervenka","sequence":"additional","affiliation":[{"name":"Centre for Experimental Medicine Institute for Clinical and Experimental Medicine  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8394-7459","authenticated-orcid":false,"given":"Barbara","family":"Szeiffov\u00e1 Ba\u010dov\u00e1","sequence":"additional","affiliation":[{"name":"Centre of Experimental Medicine Slovak Academy of Sciences, Institute for Heart Research  Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,30]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2023.07.006"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.15420\/cfr.2023.05"},{"key":"e_1_2_12_4_1","volume-title":"Heart Failure and Ejection Fraction","author":"Golla M. 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