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Reduced FID in the HS group was restored by intake of the superoxide scavenger tempol (HS + tempol in vivo group). The nitric oxide (NO) synthase inhibitor N<jats:sup>\u03c9<\/jats:sup>-nitro-l-arginine methyl ester, cyclooxygenase inhibitor indomethacin, and selective inhibitor of microsomal cytochrome P-450 epoxidase activity N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide significantly reduced FID in the low salt diet-fed group, whereas FID in the HS group was mediated by NO only. Cyclooxygenase-2 mRNA (but not protein) expression was decreased in the HS and HS + tempol in vivo groups. Hypoxia-inducible factor-1\u03b1 and VEGF protein levels were increased in the HS group but decreased in the HS + tempol in vivo group. Assessment by direct fluorescence of middle cerebral arteries under flow revealed significantly reduced vascular NO levels and increased superoxide\/reactive oxygen species levels in the HS group. These results suggest that HS intake impairs FID and changes FID mechanisms to entirely NO dependent, in contrast to the low-salt diet-fed group, where FID is NO, prostanoid, and epoxyeicosatrienoic acid dependent. These changes were accompanied by increased lipid peroxidation products in the plasma of HS diet-fed rats, increased vascular superoxide\/reactive oxygen species levels, and decreased NO levels, together with increased expression of hypoxia-inducible factor-1\u03b1 and VEGF.<\/jats:p><jats:p>NEW &amp; NOTEWORTHY High-salt (HS) diet changes the mechanisms of flow-induced dilation in rat middle cerebral arteries from a combination of nitric oxide-, prostanoid-, and epoxyeicosatrienoic acid-dependent mechanisms to, albeit reduced, a solely nitric oxide-dependent dilation. In vivo reactive oxygen species scavenging restores flow-induced dilation in HS diet-fed rats and ameliorates HS-induced increases in the transcription factor hypoxia-inducible factor-1\u03b1 and expression of its downstream target genes.<\/jats:p>","DOI":"10.1152\/ajpheart.00097.2018","type":"journal-article","created":{"date-parts":[[2018,6,15]],"date-time":"2018-06-15T19:15:36Z","timestamp":1529090136000},"page":"H718-H730","source":"Crossref","is-referenced-by-count":18,"title":["High salt intake shifts the mechanisms of flow-induced dilation in the middle cerebral arteries of Sprague-Dawley rats"],"prefix":"10.1152","volume":"315","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3374-8512","authenticated-orcid":false,"given":"Anita","family":"Matic","sequence":"first","affiliation":[{"name":"Department of Physiology and Immunology, Faculty of Medicine Osijek, Josip Juraj Strossmayer of Osijek, Osijek, 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