{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:33:29Z","timestamp":1790883209756,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2016,6,16]],"date-time":"2016-06-16T00:00:00Z","timestamp":1466035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Recent studies have shown that high salt (HS) intake leads to endothelial dysfunction and impaired vascular reactivity in different vascular beds in both animal and human models, due to increased oxidative stress.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The objective of this study was to assess vascular response to flow\u2010induced dilatation (FID) and to elucidate the role of vascular oxidative stress\/antioxidative capacity in middle cerebral arteries (MCAs) of HS\u2010fed rats <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The novelty of this study is in demonstrating impaired flow\u2010induced dilatation of MCAs and down\u2010regulation of vascular antioxidant genes with HS intake, leading to increased levels of oxidative stress in blood vessels and peripheral lymph organs, which together contribute to impaired FID.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In addition, results show increased oxidative stress in leukocytes of peripheral lymph organs, suggesting the occurrence of inflammatory processes due to HS intake.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Recirculation of leukocytes might additionally increase vascular oxidative stress <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>The aim of this study was to determine flow\u2010induced dilatation (FID) and the role of oxidative stress\/antioxidative capacity in isolated, pressurized middle cerebral arteries (MCAs) of high salt (HS)\u2010fed rats. Healthy male Sprague\u2010Dawley rats (11\u00a0weeks old) were fed low salt (0.4% NaCl; LS group) or high salt (4% NaCl; HS group) diets for 1\u00a0week. Reactivity of MCAs in response to stepwise increases in pressure gradient (\u039410\u2013\u0394100\u00a0mmHg) was determined in the absence or presence of the superoxide dismutase (SOD) mimetic TEMPOL and\/or the nitric oxide synthases (NOS) inhibitor <jats:italic>N<\/jats:italic><jats:sup>\u03c9<\/jats:sup>\u2010nitro\u2010<jats:sc>l<\/jats:sc>\u2010arginine methyl ester (<jats:sc>l\u2010NAME<\/jats:sc>). mRNA levels of antioxidative enzymes, NAPDH\u2010oxidase components, inducible (iNOS) and endothelial nitric oxide synthases (eNOS) were determined by quantitative real\u2010time PCR. Blood pressure (BP), antioxidant enzymes activity, oxidative stress in peripheral leukocytes, lipid peroxidation products and the antioxidant capacity of plasma were measured for both groups. FID was reduced in the HS group compared to the LS group. The presence of TEMPOL restored dilatation in the HS group, with no effect in the LS group. Expression of glutathione peroxidase 4 (GPx4) and iNOS in the HS group was significantly decreased; oxidative stress was significantly higher in the HS group compared to the LS group. HS intake significantly induced basal reactive oxygen species production in the leukocytes of mesenteric lymph nodes and splenocytes, and intracellular production after stimulation in peripheral lymph nodes. Antioxidant enzyme activity and BP were not affected by HS diet. Low GPx4 expression, increased superoxide production in leukocytes, and decreased iNOS expression are likely to underlie increased oxidative stress and reduced nitric oxide bioavailability, leading to impairment of FID in the HS group without changes in BP values.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp272297","type":"journal-article","created":{"date-parts":[[2016,4,10]],"date-time":"2016-04-10T18:13:40Z","timestamp":1460312020000},"page":"4917-4931","source":"Crossref","is-referenced-by-count":50,"title":["Attenuated flow\u2010induced dilatation of middle cerebral arteries is related to increased vascular oxidative stress in rats on a short\u2010term high salt diet"],"prefix":"10.1113","volume":"594","author":[{"given":"Anita","family":"Cosic","sequence":"first","affiliation":[{"name":"Department of Physiology and Immunology Faculty of Medicine J. J. 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