Chronic NaHS treatment decreases oxidative stress and improves endothelial function in diabetic mice

Ng, H. H., Yildiz, G. S., Ku, J. M., Miller, A. A. , Woodman, O. L. and Hart, J. L. (2017) Chronic NaHS treatment decreases oxidative stress and improves endothelial function in diabetic mice. Diabetes and Vascular Disease Research, 14(3), pp. 246-253. (doi: 10.1177/1479164117692766) (PMID:28467198)

Abstract

Hydrogen sulphide (H2S) is endogenously produced in vascular tissue and has anti-oxidant and vasoprotective properties. This study investigates whether chronic treatment using the fast H2S 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Miller, Dr Alyson
• Authors: Ng, H. H., Yildiz, G. S., Ku, J. M., Miller, A. A., Woodman, O. L., and Hart, J. L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Diabetes and Vascular Disease Research
• Publisher: SAGE
• ISSN: 1479-1641
• ISSN (Online): 1752-8984
• Published Online: 01 February 2017