{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:27:35Z","timestamp":1782451655973,"version":"3.54.5"},"reference-count":45,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T00:00:00Z","timestamp":1660608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Grant Agency of the Ministry of Education, Science, Research, and Sport of the Slovak Republic","award":["VEGA 2\/0111\/19"],"award-info":[{"award-number":["VEGA 2\/0111\/19"]}]},{"name":"Scientific Grant Agency of the Ministry of Education, Science, Research, and Sport of the Slovak Republic","award":["VEGA 2\/0132\/20"],"award-info":[{"award-number":["VEGA 2\/0132\/20"]}]},{"name":"Scientific Grant Agency of the Ministry of Education, Science, Research, and Sport of the Slovak Republic","award":["VEGA 2\/0147\/22"],"award-info":[{"award-number":["VEGA 2\/0147\/22"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Increased fructose consumption induces metabolic-syndrome-like pathologies and modulates vasoactivity and the participation of nitric oxide (NO) and hydrogen sulfide (H2S). We investigated whether a slow-releasing H2S donor, GYY-4137, could exert beneficial activity in these conditions. We examined the effect of eight weeks of fructose intake on the blood pressure, biometric parameters, vasoactive responses, and NO and H2S pathways in fructose-fed spontaneously hypertensive rats with or without three weeks of GYY-4137 i.p. application. GYY-4137 reduced triacylglycerol levels and blood pressure, but not adiposity, and all were increased by fructose intake. Fructose intake generally enhanced endothelium-dependent vasorelaxation, decreased adrenergic contraction, and increased protein expression of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF\u03b1), and concentration of conjugated dienes in the left ventricle (LV). Although GYY-4137 administration did not affect vasorelaxant responses, it restored disturbed contractility, LV oxidative damage and decreased protein expression of TNF\u03b1 in fructose-fed rats. While the participation of endogenous H2S in vasoactive responses was not affected by fructose treatment, the expression of H2S-producing enzyme cystathionine \u03b2-synthase in the LV was increased, and the stimulation of the NO signaling pathway improved endothelial function in the mesenteric artery. On the other hand, chronic treatment with GYY-4137 increased the expression of H2S-producing enzyme cystathionine \u03b3-lyase in the LV and stimulated the beneficial pro-relaxant and anti-contractile activity of endogenous H2S in thoracic aorta. Our results suggest that sulfide and nitroso signaling pathways could trigger compensatory vasoactive responses in hypertensive rats with metabolic disorder. A slow H2S-releasing donor could partially amend metabolic-related changes and trigger beneficial activity of endogenous H2S.<\/jats:p>","DOI":"10.3390\/ijms23169215","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T23:44:25Z","timestamp":1660693465000},"page":"9215","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Vasoactive Effects of Chronic Treatment with Fructose and Slow-Releasing H2S Donor GYY-4137 in Spontaneously Hypertensive Rats: The Role of Nitroso and Sulfide Signalization"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3108-238X","authenticated-orcid":false,"given":"Andrea","family":"Berenyiova","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\/0000-0003-0132-670X","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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basak Gunes","family":"Aydemir","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"}]},{"given":"Samuel","family":"Golas","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\/0000-0001-8748-4279","authenticated-orcid":false,"given":"Miroslava","family":"Majzunova","sequence":"additional","affiliation":[{"name":"Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, 841-04 Bratislava, Slovakia"},{"name":"Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius University, 841-04 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[[2022,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.4196\/kjpp.2020.24.4.319","article-title":"Activation of the Renin-Angiotensin System in High Fructose-Induced Metabolic Syndrome","volume":"24","author":"Kim","year":"2020","journal-title":"Korean J. 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