engleski

Effect of high salt diet on expression of antioxidative enzymes, hypoxia inducible factor 1 alpha and cyclooxygenase 1 and 2 in blood vessels of Sprague-Dawley rats

Low-dose angiotensin II (ANG II) infusion restores impaired vascular relaxation responses to acetylcholine and hypoxia in high salt fed rats and increases Cu/Zn SOD expression in genetically modified HS fed rats. Decreased Cu/Zn- and Mn- superoxide dismutase protein expression in cerebral vessels of Dahl Salt-Sensitive rats is associated with increased oxidative stress and impaired vasodilator responses mediated via cyclooxygenases (COX). The aim of this study was to assess the effects of 1 week high salt diet (HS ; 4% NaCl) on antioxidative enzymes (Cu/Zn SOD, MnSOD, EC-SOD, catalase (CAT) and glutathione- peroxidase 4 (GPx4)), cyclooxygenase 1 and 2 (COX 1, 2) and hypoxia inducible factor 1 alpha (HIF-1α) gene expression in blood vessels. 11-weeks old healthy male Sprague-Dawley rats (N=14) were divided into control group fed with standard rat chow (0.4% NaCl) and HS group fed (4% NaCl) for 1 week. Following diet protocol, rats were anesthetized with ketamine (75 mg/kg) and midazolam (2.5 mg/kg), decapitated and their aorta and brain blood vessels harvested. Superoxide dismutase isoforms (Cu/Zn SOD, MnSOD, EC-SOD), HIF1α, COX 1, 2, GPx4, and catalase mRNA levels were determined by quantitative real-time PCR. Data were analyzed using SigmaPlot 11.0 and p<0.05 was considered significant. All experimental procedures conformed to the EU Guidelines for the Care and Use of Laboratory Animals (directive 86/609) and were approved by the local Ethical CommitteeRESULTS: Significantly higher expression of HIF-1α (p=0.002), COX1 (p=0.002), COX2 (p=0.002), GPX4 (p=0.015), Cu/Zn SOD (p=0.018), MnSOD (p=0.001) and EC-SOD (p=0, 001) were in aortas compared to cerebral vessels of control rats. HS rats had significantly down-regulated HIF-1α in aortas (p=0.037) and COX2 in cerebral blood vessels (p = 0.011) compared to controls. Furthermore, HS group had significantly decreased mRNA level of GPx4 (p=0.012) and Cu/Zn SOD (p=0.009), and increased level of COX1 (p=0.030) in aortas compared to aortas of controls. Cu/Zn SOD was significantly decreased (p=0, 009) in aorta of HS rats compared to controls. Catalase, EC-SOD and MnSOD gene expression was reduced in HS rats but did not reach statistical significance (p=0.054, p=0.055 and p=0.069, respectively) HS diet down-regulated HIF-1α and COX2 gene in aortas and cerebral blood vessels. All antioxidative enzymes genes were down-regulated by HS. These results suggest that HS may promote oxidative stress by reducing antioxidative capacity through HIF-1α and antioxidative gene expression modulation. In addition, there is altered expression of genes important in mediating functional vascular responses (i.e. COX1, 2) by HS diet.

high salt diet; antioxidative enzymes; hypoxia inducible factor 1; cyclooxygenase 1 and 2; blood vessels

nije evidentirano