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Despite long-term research, new interventions are still being sought to improve cardiovascular disorders associated with metabolic syndrome. Methods: To explore the therapeutic potential of a slow-releasing H2S donor, we evaluated the effects of 3 weeks of treatment with GYY-4137 on systolic blood pressure (sBP), cardiac parameters, adiposity, selected plasma markers, and the vascular function of the thoracic aortas (TAs) and mesenteric arteries (MAs) isolated from male spontaneously hypertensive rats (SHRs) fed an HFD for 8 weeks. Results: HFD administration induced cardiac remodeling, increased adiposity, and decreased adrenergic contractility in both TAs and MAs. Moreover, although high-fat intake improved TAs relaxation, it decreased aortic protein expression of endothelial NO synthase and the involvement of NO in vasoactive responses of both TAs and MAs. In addition, protein expression of inducible NOS and tumor necrosis factor alpha (TNF\u03b1) in aortas was increased, as were plasma levels of chemerin, which has been proposed as a possible link among metabolic and vascular disorders and inflammation. Treatment with GYY-4137 reduced sBP, improved relaxation of the MAs, partially restored the contractility of the TAs, generally restored NO signaling, and decreased the protein expression of the inducible NOS and TNF\u03b1, as well as plasma chemerin levels. Conclusions: A slow H2S-releasing donor could partially ameliorate the metabolic changes induced by increased fat intake during essential hypertension and trigger beneficial vasoactive effects associated with the NO signaling restoration and suppression of inflammation.<\/jats:p>","DOI":"10.3390\/pathophysiology32020027","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T04:08:06Z","timestamp":1750219686000},"page":"27","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Slow Hydrogen Sulfide Donor GYY-4137 Partially Improves Vascular Function in Spontaneously Hypertensive Rats Fed a High-Fat Diet"],"prefix":"10.3390","volume":"32","author":[{"given":"Basak G.","family":"Aydemir","sequence":"first","affiliation":[{"name":"Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3108-238X","authenticated-orcid":false,"given":"Andrea","family":"Berenyiova","sequence":"additional","affiliation":[{"name":"Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia"},{"name":"Institute of Pathophysiology, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0132-670X","authenticated-orcid":false,"given":"Martina","family":"Cebova","sequence":"additional","affiliation":[{"name":"Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia"},{"name":"Institute of Pathophysiology, Faculty of Medicine, Comenius University, 811 08 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8546-1655","authenticated-orcid":false,"given":"John D.","family":"Henderson","sequence":"additional","affiliation":[{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, DK-2200 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrej","family":"Barta","sequence":"additional","affiliation":[{"name":"Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0483-7468","authenticated-orcid":false,"given":"Sona","family":"Cacanyiova","sequence":"additional","affiliation":[{"name":"Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"key":"ref_1","unstructured":"(2024, December 11). 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