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High salt intake shifts the mechanisms of flow- induced dilation in the middle cerebral arteries of Sprague-Dawley rats

The goal of this study was to examine the effect of 1-week 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 (MCA) of male Sprague-Dawley rats (N=15-16/per group). Reduced FID in the HS group was restored by intake of the superoxide scavenger TEMPOL (HS+TEMPOL in vivo group). Nitric oxide synthases (NOS) inhibitor Nω-nitro-L-arginine methyl ester (L-NAME), COX inhibitor indomethacin (INDO) and selective inhibitor of microsomal CYP450 epoxidase activity N- (methylsulfonyl)-2-(2-propynyloxy)- benzenehexanamide (MS-PPOH) significantly reduced FID in the LS group, while FID in the HS group was mediated by NO only. COX-2 mRNA (but not protein) expression was decreased in the HS and HS+TEMPOL in vivo groups. HIF-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 MCA 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 LS group where FID is NO, prostanoid and epoxyeicosatrienoic acids (EET's) dependent. Those changes were accompanied by increased lipid peroxidation products in the plasma of HS-fed rats, increased vascular superoxide/reactive oxygen species levels and decreased NO levels ; together with increased expression of HIF-1α and VEGF.

flow-induced dilation, HIF-1α, high salt diet, oxidative stress, TEMPOL

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