engleski

Angiotensin II Infusion Changes Hypoxia- Inducible Factor 1 (HIF-1) And Its Accompanying Genes Expression in Cerebral Microcirculation of High Salt Fed Sprague-Dawley Rats

Recently we showed that superoxide scavenging increases HIF-1αantioxidative enzymes’ genes expression in cerebral circulation of rats fed high salt (HS) diet, suggesting that HIF-1α expression depends on the level of oxidative stress. Also, suppressor doses of angiotensin II (ANGII) restored NO production and increased antioxidant capacity in HS fed rats. This study aimed to assess the role of ANGII on HIF-1 alpha and its target genes’ expression in rats fed HS diet. Healthy male Sprague-Dawley rats, 9-11 weeks old, were assigned in 3 groups (n=6- 8 rats/group): low salt-diet group (LS group, 0.4%NaCl in rat chow) ; HS group (1 week of 4%NaCl in rat chow) and HS+ANGII group (1 week of HS diet, 4th-7th day infused by subpressor doses of ANGII via osmotic minipump (100ng/kg/min/3 days). Afterwards, rats were anesthetizedwith ketamine (75mg/kg) and midazolam (2.5mg/kg) and decapitated. mRNA expression of HIF-1 alpha, PHD1, 2 and 3, eNOS, iNOS, and HPRT were measured in cerebral microcirculation, by rtPCR. All experimental procedures were approved by the local Ethical Committee and conformed to the EU Directive 86/609. Data were analyzed using One-Way ANOVA, presented as mean±SD. p<0.05 was considered significant. Relative gene expression of HIF-1 alpha, PHD1, PHD2 and PHD3 was significantly increased in HS+ANGII group compared to other groups (p<0.05). iNOS expression was significantly increased in HS+ANGII group compared to HS group. eNOS gene expression was not changed (p>0.05). Results suggest that increase in HIF-1 alpha and its accompanying genes is related to decreased oxidative stress in the vasculature due to ANGII infusion. Results support pivotal role of ANGII in maintaining endothelial function by affecting signaling pathways. This work was supported by Croatian Science Foundation Project IP-2014-09- 6380 (Faculty of Medicine, Osijek, Croatia).

High-Salt Diet ; Angiotensin II ; Cerebral Circulation ; Hypoxia-Inducible Factor 1 (HIF-1)

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