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

Abstract

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 N-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.

Short-Term High-NaCl Dietary Intake Changes Leukocyte Expression of VLA-4, LFA-1, and Mac-1 Integrins in Both Healthy Humans and Sprague-Dawley Rats: A Comparative Study

“…Similarly, we previously demonstrated increased leukocytes' reactive oxygen species production after HS intake in normotensive Sprague-Dawley rats [12]. Thus, it may be suggested that leukocyte-endothelial adhesion in response to HS loading is multifactorial, and the role of the RAS becomes apparent along with progression of vascular damage [12, 14].…”

“…Similarly, impaired suppressive Treg function during HS load contributes to augmented Th1/Th17-mediated inflammation in autoimmune disease [11]. Interestingly, excessive salt intake has been linked to increased oxidative stress [12–14], aggravated inflammation, and pathophysiological differentiation of monocytes leading to organ damage even in treated hypertensive patients, suggesting a blood pressure-independent effect [15–18].…”

Leukocyte Activation and Antioxidative Defense Are Interrelated and Moderately Modified by n-3 Polyunsaturated Fatty Acid-Enriched Eggs Consumption—Double-Blind Controlled Randomized Clinical Study

“…Lipids extraction in plasma samples was performed as previously described [ 26 ]. The concentrations of LOOH were calculated using the molar absorptivity of the complex [FeNCS] 2+ formed per mol of LOOH, 58,440 M −1 cm −1 , at 500 nm [ 27 , 28 ]. Measurements were performed in the Laboratory for Radiation Chemistry and Dosimetry, Ruđer Bošković Institute, Zagreb, Croatia.…”

Arachidonic Acid Metabolites of CYP450 Enzymes and HIF-1α Modulate Endothelium-Dependent Vasorelaxation in Sprague-Dawley Rats under Acute and Intermittent Hyperbaric Oxygenation

“…Blood pressure measurement was performed using established protocols, as previously described [ 18 , 29 , 54 , 55 ]. Briefly, pressure values were measured using the Spacelabs Medical system (Spacelabs Medical, Inc., Redmond, WA, USA) using the PE-50 catheter inserted into the left femoral artery.…”

“…The Western blot was made according to the established method of our laboratory [ 9 , 55 ]. The same Western blot protocol was used to determine the COX-1, COX-2, iNOS, HIF-1α, VEGF and CYP2c11 protein expression in the rat aortas, deeply frozen immediately after isolation.…”