Folic acid reverses endothelial dysfunction induced by inhibition of tetrahydrobiopterin biosynthesis

Moat, Stuart James, Clarke, Zoe L., Madhavan, Anil Kumar, Lewis, Malcolm John and Lang, Derek 2006. Folic acid reverses endothelial dysfunction induced by inhibition of tetrahydrobiopterin biosynthesis. European Journal of Pharmacology 530 (3) , pp. 250-258. 10.1016/j.ejphar.2005.11.047

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Abstract

While folic acid has been shown to reverse endothelial dysfunction, the exact underlying mechanism remains elusive. Here, folic acid reversed both the endothelial dysfunction and increased production of superoxide following depletion of rabbit aortic ring tetrahydrobiopterin (BH4) levels with 2,4-diamino-6-hydroxy-pyrimidine (DAHP) and N-acetyl-5-hydroxy-tryptamine (NAS). Incubation with l-nitroarginine methyl ester also attenuated the production of superoxide. DAHP and NAS reduced BH4 concentrations in both aorta and cultured porcine aortic endothelial cells. Folic acid had no effect on BH4 concentrations in either preparation. The superoxide anion scavenger Tiron but not folic acid reversed the endothelial dysfunction produced in aortic rings by inhibition of copper-zinc superoxide dismutase with diethyldithiocarbamic acid. Neither folic acid nor its metabolite 5-methyltetrahydrofolate prevented the in vitro oxidation of BH4. This study demonstrates that folic acid reverses the endothelial dysfunction induced by BH4 depletion independently of either the regeneration or stabilization of BH4 or an antioxidant effect.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Uncontrolled Keywords:	Folic acid; Endothelium; Tetrahydrobiopterin; Endothelial dysfunction
Publisher:	Elsevier
ISSN:	0014-2999
Last Modified:	04 Jun 2017 01:30
URI:	https://orca.cardiff.ac.uk/id/eprint/46

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