Current address: Department of Pharmacology & Therapeutics, 3330, Hospital Drive (N.W.), Calgary, Alberta, Canada T2N 4N1
Chronic oral supplementation with sepiapterin prevents endothelial dysfunction and oxidative stress in small mesenteric arteries from diabetic (db/db) mice
Article first published online: 2 FEB 2009
2003 British Pharmacological Society
British Journal of Pharmacology
Volume 140, Issue 4, pages 701–706, October 2003
How to Cite
Pannirselvam, M., Simon, V., Verma, S., Anderson, T. and Triggle, C. R. (2003), Chronic oral supplementation with sepiapterin prevents endothelial dysfunction and oxidative stress in small mesenteric arteries from diabetic (db/db) mice. British Journal of Pharmacology, 140: 701–706. doi: 10.1038/sj.bjp.0705476
- Issue published online: 2 FEB 2009
- Article first published online: 2 FEB 2009
- (Received May 20, 2003, Revised July 2, 2003, Accepted July 25, 2003)
- Endothelial dysfunction;
- type II diabetes;
- oxidative stress;
- db/db mice
We previously reported that acute incubation with tetrahydrobiopterin (BH4) or sepiapterin, a cofactor for endothelial nitric oxide synthase and a stable precursor of BH4, respectively, enhanced the acetylcholine (Ach)-induced relaxation of isolated small mesenteric arteries (SMA) from diabetic (db/db) mice. In this study, we investigated the effect of chronic oral supplementation of sepiapterin (10 mg kg−1 day−1) to db/db mice on endothelium function, biopterin levels and lipid peroxidation in SMA.
Oral dietary supplementation with sepiapterin had no effect on glucose, triglyceride, cholesterol levels and body weight. SMA from db/db mice showed enhanced vascular reactivity to phenylephrine, which was corrected with sepiapterin supplementation. Furthermore, Ach, but not sodium nitroprusside-induced relaxation, was improved with sepiapterin supplementation in db/db mice.
BH4 levels and guanosine triphosphate cyclohydrolase I activity in SMA were similar in db/+ and db/db mice. Sepiapterin treatment had no effects on BH4 or guanosine triphosphate cyclohydrolase I activity. However, the level of dihydrobiopterin+biopterin was higher in SMA from db/db mice, which was corrected following sepiapterin treatment.
Thiobarbituric acid reactive substance, malondialdehyde, a marker of lipid peroxidation, was higher in SMA from db/db mice, and was normalized by sepiapterin treatment.
These results indicate that sepiapterin improves endothelial dysfunction in SMA from db/db mice by reducing oxidative stress. Furthermore, these results suggest that decreased biosynthesis of BH4 may not be the basis for endothelial dysfunction in SMA from db/db mice.
British Journal of Pharmacology (2003) 140, 701–706. doi:10.1038/sj.bjp.0705476