{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:43:30Z","timestamp":1791287010747,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,6,16]],"date-time":"2017-06-16T00:00:00Z","timestamp":1497571200000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007351","name":"Secretaria de Ciencia y Tecnica, Universidad de Buenos Aires","doi-asserted-by":"publisher","award":["20020130100019BA"],"award-info":[{"award-number":["20020130100019BA"]}],"id":[{"id":"10.13039\/501100007351","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Auton Autocoid Pharmacol"],"published-print":{"date-parts":[[2017,6]]},"abstract":"Summary<\/jats:title>Perivascular adipose tissue dysfunction induced by high\u2010fat feeding leads to alterations in the modulation of inflammation, contractile activity of the vascular smooth muscle and endothelial function, all risk factors in the development of hypertension. Metformin, an activator ofAMP<\/jats:styled-content>\u2010activated protein kinase (AMPK<\/jats:styled-content>), is currently the first\u2010line drug treatment for type 2 diabetes (T2DM<\/jats:styled-content>) and metabolic syndrome. Besides its glucose\u2010lowering effect, there is an interest in actions of this drug with potential relevance in cardiovascular diseases.<\/jats:p><\/jats:list-item>The high\u2010fat (HF<\/jats:styled-content>) diet is an experimental model that resembles human metabolic syndrome. We have previously reported an altered pattern of prostanoid release in mesenteric vessels in this model.<\/jats:p><\/jats:list-item>The aim of this study was to analyse the effects of metformin on mesenteric vascular bed prostanoid release, adiposity index and its relation to blood pressure in Sprague\u2010Dawley rats fed aHF<\/jats:styled-content>diet for 8 and 12 weeks. Eight groups were used: control (C8, C1),HF<\/jats:styled-content>diet (HF<\/jats:styled-content>8,HF<\/jats:styled-content>12, 50% w\/w bovine fat), metformin\u2010treated (CM<\/jats:styled-content>f8,CM<\/jats:styled-content>f12, 500\u00a0mg\/kg\/day) and metformin\u2010treatedHF<\/jats:styled-content>diet (HFM<\/jats:styled-content>f8,HFM<\/jats:styled-content>f12, both treatments).<\/jats:p><\/jats:list-item>HF<\/jats:styled-content>diet increased mesenteric vascular bed adiposity index (%,HF<\/jats:styled-content>8: 1.7\u00b10.1 vs C8: 0.9\u00b10.04 andHF<\/jats:styled-content>12: 1.8\u00b10.1 vs C12: 0.8\u00b10.1,P<\/jats:italic><.001); systolic blood pressure (SBP<\/jats:styled-content>, mm Hg,HF<\/jats:styled-content>8: 145\u00b16 vs C8: 118\u00b14,P<\/jats:italic><.01 andHF<\/jats:styled-content>12: 151\u00b11 vs C12: 121\u00b13,P<\/jats:italic><.001). We found a positive correlation between these two parameters. MoreoverHF<\/jats:styled-content>diet increased the release of vasoconstrictor prostanoids such as thromboxane (TX<\/jats:styled-content>) B2<\/jats:sub>(ngPR<\/jats:styled-content>\/mg of tissue,HF<\/jats:styled-content>8: 117\u00b16 vs C8: 66\u00b12 andHF<\/jats:styled-content>12: 123\u00b16 vs C12: 62\u00b15,P<\/jats:italic><.001) and prostaglandin (PG<\/jats:styled-content>) F2\u03b1<\/jats:sub>(ng\/mg,HF<\/jats:styled-content>8: 153\u00b19 vs C8: 88\u00b13 andHF<\/jats:styled-content>12: 160\u00b111 vs C12: 83\u00b15,P<\/jats:italic><.001). We also found that this increase in the release of vasoconstrictor prostanoids positively correlates with the elevation ofSBP<\/jats:styled-content>. In addition,HF<\/jats:styled-content>diet increases the release of PGE2<\/jats:sub>and decreases the prostacyclin (PGI<\/jats:styled-content>2<\/jats:sub>)\/TXA<\/jats:styled-content>2<\/jats:sub>release ratio at 8 and 12\u00a0weeks of treatment compared to control groups.<\/jats:p><\/jats:list-item>In theHFM<\/jats:styled-content>f group, metformin treatment prevented all these increases in mesenteric vascular bed adiposity index (%,HFM<\/jats:styled-content>f8: 1.3\u00b10.2 vsHF<\/jats:styled-content>8 andHFM<\/jats:styled-content>f12: 1.3\u00b10.1 vsHF<\/jats:styled-content>12,P<\/jats:italic><.05);SBP<\/jats:styled-content>(mm Hg,HFM<\/jats:styled-content>f8: 127\u00b12 vsHF<\/jats:styled-content>8 andHFM<\/jats:styled-content>f12: 132\u00b11 vsHF<\/jats:styled-content>12,P<\/jats:italic><.001);TXB<\/jats:styled-content>2<\/jats:sub>release (ngPR<\/jats:styled-content>\/mg of tissue,HFM<\/jats:styled-content>f8: 65\u00b112 vsHF<\/jats:styled-content>8,P<\/jats:italic><.05 andHFM<\/jats:styled-content>f12: 53\u00b13 vsHF<\/jats:styled-content>12,P<\/jats:italic><.001) andPGF<\/jats:styled-content>2<\/jats:sub>\u03b1 (ngPR<\/jats:styled-content>\/mg of tissue,HFM<\/jats:styled-content>f8: 99\u00b113 vsHF<\/jats:styled-content>8,P<\/jats:italic><.01 andHFM<\/jats:styled-content>f12: 77\u00b18 vsHF<\/jats:styled-content>12,P<\/jats:italic><.001). Meanwhile metformin prevented the increment inPGE<\/jats:styled-content>2<\/jats:sub>release only at 12\u00a0weeks. On the other hand, metformin improved the PGI2<\/jats:sub>\/TXA2<\/jats:sub>ratio in both periods studied.<\/jats:p><\/jats:list-item>In conclusion, metformin could exert beneficial effects on adipose tissue and the vascular system by improving endothelial dysfunction induced by an imbalance of vasoactive substances in mesenteric perivascular adipose tissue in this model.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p>","DOI":"10.1111\/aap.12057","type":"journal-article","created":{"date-parts":[[2017,6,16]],"date-time":"2017-06-16T09:17:34Z","timestamp":1497604654000},"page":"37-43","source":"Crossref","is-referenced-by-count":19,"title":["Metformin prevents vascular prostanoid release alterations induced by a high\u2010fat diet in rats"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9297-0121","authenticated-orcid":false,"given":"H. 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