engleski

Influence of high-salt diet on HIF-1alpha and antioxidative enzymes mRNA expression in blood vessels on young male Sprague-Dawley rats

OBJECTIVE Recent data on Dahl Salt-Sensitive rats demonstrated decreased Cu/Zn- and Mn- superoxide dismutase protein expression in cerebral vessels, leading to increased oxidative stress and impaired vasodilator responses. High salt diet (HSD) per se increases vascular oxidative stress, and the high levels of superoxide increase hypoxia- inducible factor 1-alpha (HIF-1α) protein expression in kidneys. The aim of this study was to assess the influence of feeding 3 weeks old rats with HSD (4% NaCl) for 1 week on HIF- 1α mRNA expression in blood vessels and its relationship to antioxidative enzymes gene expression. DESIGN AND METHODS: 3-weeks old healthy male Sprague-Dawley rats (N=6), after weaning were divided into 2 groups: 1-week-HSD group and an age and sex matched control group fed with standard rat chow (0.4% NaCl). Following diet protocol, rats were sacrificed and their aorta and cerebral blood vessels harvested for HIF-1α, Cu/Zn SOD, MnSOD, EC-SOD and glutathione-peroxidase 1 and 4 (GPx1, GPx4) mRNA expression analysis by Real-time PCR. Data were analyzed using REST 2009 software and p<0.05 was considered significant. RESULTS: 1- week-HSD rats presented with significant downregulation of Cu/Zn SOD (P=0, 014), MnSOD (P=0, 002) and EC-SOD (P= 0, 037) genes in cerebral blood vessels, and EC-SOD in aorta (P=0, 005) compared to control group. GPx4 mRNA level was significantly decreased in aorta (P=0, 019) and cerebral blood vessels (P=0, 018) of 1-week- HSD rats compared to control group. There was no significant difference in GPx1 gene expression between the groups. HIF-1α expression in cerebral blood vessels was 5, 25 (p=0, 003) fold higher in 1-week-HSD rats compared to control group. CONCLUSIONS: Our results imply that HSD induces downregulation of antioxidative enzyme genes’ in blood vessels of very young rats. These effects are immediate, resulting in decreased mRNA level of SODs and GPx4 already after 7 days of HSD. Parallel to these changes we found increased HIF- 1α expression, suggesting possible mutual transcriptional regulation.

high salt diet; antioxidant enzymes

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