High salt intake shifts the mechanisms of flow-induced dilation in the middle cerebral arteries of Sprague-Dawley rats. Am J Physiol Heart Circ Physiol 2018 Sep 01;315(3):H718-H730
Date
06/16/2018Pubmed ID
29906224DOI
10.1152/ajpheart.00097.2018Scopus ID
2-s2.0-85058153813 (requires institutional sign-in at Scopus site) 14 CitationsAbstract
The goal of the present study was to examine the effect of 1 wk of high salt (HS) intake and the role of oxidative stress in changing the mechanisms of flow-induced dilation (FID) in isolated pressurized middle cerebral arteries of male Sprague-Dawley rats ( n = 15-16 rats/group). 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 Nω-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-1α 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-1α and VEGF. NEW & 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-1α and expression of its downstream target genes.
Author List
Matic A, Jukic I, Stupin A, Baric L, Mihaljevic Z, Unfirer S, Tartaro Bujak I, Mihaljevic B, Lombard JH, Drenjancevic IMESH terms used to index this publication - Major topics in bold
AnimalsCerebrovascular Circulation
Cyclooxygenase 2
Cyclooxygenase Inhibitors
Hypoxia-Inducible Factor 1, alpha Subunit
Indomethacin
Male
Middle Cerebral Artery
NG-Nitroarginine Methyl Ester
Nitric Oxide
Rats
Rats, Sprague-Dawley
Sodium, Dietary
Superoxides
Vascular Endothelial Growth Factor A
Vasodilation