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The role of oxidative stress in development of impaired vascular response under the influence of high salt intake in Sprague-Dawley rats

Introduction: This study aimed to determine the in vitro flow-induced dilatation (FID) mechanisms of middle cerebral artery (MCA), the expression of antioxidative genes, genes involved in dilatation pathways, level of leukocyte activation and the role of oxidative stress in Sprague-Dawley (SD) rats on a high salt (HS) diet. Methods: 11-weeks old healthy male SD rats were divided in low salt group (LS) given standars rat chow (0.4%NaCl) and HS group given food containing 4%NaCl for 1 week with/without superoxide dismutase (SOD) mimetic TEMPOL in vivo. MCA reactivity in response to FID in the absence/presence of inhibitors L-NAME, INDO, MS-PPOH and TEMPOL in vitro was examined. mRNA levels of enzymes from brain blood vessels were determined with rtPCR. Leukocyte activation and level of oxidative stress in leukocytes from blood and peripheral organs were mesured by flow cytometry. Blood pressure, lipid peroxidation products and antioxidative capacity were also measured. Results: FID was reduced in HS group compared to LS group. Inhibitors (independantly) significantly reduced FID in LS group. FID in HS group was mediated by NO. TEMPOL restored FID in HS group to basal level. Expression of GPx4 and iNOS in HS group was significantly decreased. Antioxidant enzymes activity and BP were not affected by HS diet. HS intake significantly increased basic reactive oxygen species (ROS) production in the leukocytes of mesenteric lymph nodes and splenocytes, and intracellular production after stimulation in peripheral lymph nodes. Discussion: Mechanisms of FID are different in LS and HS groups. Low GPx4 expression, increased superoxide production in leukocytes, together with decreased iNOS expression underlies increased oxidative stress and reduced NO bioavailability in HS group, which caused impairment of FID in HS group without changes in BP. Conclusion: FID in HS diet is determined by synthesis of ROS in the vascular wall and affects vascular reactivity mechanisms.

antioxidative enzymes; flow-induced dilation; high salt diet; middle cerebral artery; oxidative stress

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