| Autor: |
Ng HH; 1 School of BioSciences, University of Melbourne, Parkville, VIC, Australia., Yildiz GS; 2 School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia., Ku JM; 2 School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia., Miller AA; 2 School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia., Woodman OL; 2 School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia., Hart JL; 2 School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC, Australia. |
| Abstrakt: |
Hydrogen sulphide (H 2 S) is endogenously produced in vascular tissue and has anti-oxidant and vasoprotective properties. This study investigates whether chronic treatment using the fast H 2 S donor NaHS could elicit a vasoprotective effect in diabetes. Diabetes was induced in male C57BL6/J mice with streptozotocin (60 mg/kg daily, ip for 2 weeks) and confirmed by elevated blood glucose and glycated haemoglobin levels. Diabetic mice were then treated with NaHS (100 µmol/kg/day) for 4 weeks, and aortae collected for functional and biochemical analyses. In the diabetic group, both endothelium-dependent vasorelaxation and basal nitric oxide (NO • ) bioactivity were significantly reduced ( p < 0.05), and maximal vasorelaxation to the NO • donor sodium nitroprusside was impaired ( p < 0.05) in aorta compared to control mice. Vascular superoxide generation via nicotine adenine dinucleotide phosphate (NADPH) oxidase ( p < 0.05) was elevated in aorta from diabetic mice which was associated with increased expression of NOX2 ( p < 0.05). NaHS treatment of diabetic mice restored endothelial function and exogenous NO • efficacy back to control levels. NaHS treatment also reduced the diabetes-induced increase in NADPH oxidase activity, but did not affect NOX2 protein expression. These data show that chronic NaHS treatment reverses diabetes-induced vascular dysfunction by restoring NO • efficacy and reducing superoxide production in the mouse aorta. |
