engleski

INCREASED OXIDATIVE STRESS UPON HIGH SALT DIET IMPAIRES FLOW-INDUCED DILATION IN SPRAGUE- DAWLEY RATS

Objective The aim of this study was to assess the effects of 1 week high salt diet (HS ; 4% NaCl) on microvascular responses to flow- induced dilation (FID) and antioxidative enzymes, cyclooxygenase 1 and 2 (COX 1, 2) and hypoxia inducible factor 1 alpha (HIF-1α) gene expression in brain blood vessels. Design and Methods 11-weeks old healthy male rats were divided in control group (N=10) and HS group SD (N=9). Middle cerebral arteries were isolated and cannulated for vascular reactivity measurements in response to stepwise increases in pressure (Δ10-Δ100), in the absence/presence of the NOS inhibitor L-NAME, COX-1, 2 inhibitor indomethacin (INDO), selective inhibitor of CYP450 epoxidase activity MS-PPOH, and superoxide dismutase mimetic TEMPOL. Superoxide dismutase isoforms (Cu/Zn SOD, MnSOD, EC-SOD), HIF1α, COX1, 2, GPx4, and catalase mRNA levels were determined from brain blood vessels (N=14) by quantitative real-time PCR. Results FID was reduced in HS group at each pressure gradient, but significantly at Δ40, and Δ100. L-NAME, INDO and MS-PPOH (independently) significantly reduced FID in the control group at each pressure gradient except Δ10. L-NAME and INDO reduced FID in HS group, reaching statistical significance for L- NAME at Δ20 and Δ40.The presence of TEMPOL restores FID in HS group to control levels at pressure gradients Δ20-Δ100, while in control group TEMPOL had no effect. 1- week-HS rats had significantly downregulated COX2 compared to controls. The expression of each antioxidant enzymes and HIF-1α gene were reduced in HS group compared to control cerebral blood vessels. Conclusion Impaired FID in HS is occurs due to reactive oxygen species produced in the vascular wall. Whereas in control rats FID is mediated with NO, and also with metabolites of COX-1, 2 and EETs, remaining reactivity to FID in HS rats was mediated by NO. HS diet may promote oxidative stress by reducing antioxidative capacity through HIF-1α and antioxidative gene expression modulation.

high salt diet; oxidative stress; flow induced dilation; rats

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