Chronic oral supplementation with sepiapterin prevents endothelial dysfunction and oxidative stress in small mesenteric arteries from diabetic (db/db) mice
| Autor: | Valerie Simon, Todd J. Anderson, Chris R. Triggle, Subodh Verma, Malarvannan Pannirselvam |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Pharmacology
medicine.medical_specialty Sepiapterin Endothelium business.industry Biopterin Tetrahydrobiopterin Malondialdehyde medicine.disease chemistry.chemical_compound medicine.anatomical_structure Endocrinology chemistry Dihydrobiopterin Internal medicine medicine Endothelial dysfunction business Mesenteric arteries medicine.drug |
| Zdroj: | British Journal of Pharmacology. 140:701-706 |
| ISSN: | 0007-1188 |
| DOI: | 10.1038/sj.bjp.0705476 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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