Vascular endothelial dysfunction: does tetrahydrobiopterin play a role?

@article{Katui2001VascularED,
  title={Vascular endothelial dysfunction: does tetrahydrobiopterin play a role?},
  author={Zvonimir S. Katu{\vs}i{\'c}},
  journal={American journal of physiology. Heart and circulatory physiology},
  year={2001},
  volume={281 3},
  pages={
          H981-6
        }
}
  • Z. Katušić
  • Published 1 September 2001
  • Biology
  • American journal of physiology. Heart and circulatory physiology
Tetrahydrobiopterin is one of the most potent naturally occurring reducing agents and an essential cofactor required for enzymatic activity of nitric oxide synthase (NOS). The exact role of tetrahydrobiopterin in the control of NOS catalytic activity is not completely understood. Existing evidence suggests that it can act as allosteric and redox cofactors. Suboptimal concentration of tetrahydrobiopterin reduces formation of nitric oxide and favors "uncoupling" of NOS leading to NOS-mediated… 

Figures and Tables from this paper

Synthesis and recycling of tetrahydrobiopterin in endothelial function and vascular disease.

Endothelial nitric oxide synthase dysfunction in diabetic mice: importance of tetrahydrobiopterin in eNOS dimerisation

The results demonstrate that BH4 plays an important role in regulating eNOS activity and its functional protein structure, suggesting that increasing endothelial BH 4 and/or protecting it from oxidation may be a rational therapeutic strategy to restore eN OS function in diabetes.

Antioxidants and endothelial nitric oxide synthesis

The data obtained in cell culture and animal studies are promising, but human long-term studies are needed to determine whether the described mechanisms are active in vivo and may provide a rationale for optimizing dietary or supplementary intake of antioxidant vitamins in certain subsets of patients.

Beneficial Role of Tetrahydrobiopterin on Various Cardiovascular Diseases and Regulation of its Levels under Pathological Conditions

Benefits of supplementation of BH4 appears to be important therapeutic strategies in vascular diseases and reperfusion injury, and induction of Bh4 synthesis may endogenous defense system against oxidative stress-mediated cardiovascular diseases.

Tetrahydrobiopterin deficiency exaggerates intimal hyperplasia after vascular injury.

It is described, for the first time, that in vivo BH4 deficiency facilitates neointimal formation after vascular injury and modulation of BH 4 bioavailability is an important therapeutic target for restenosis.

Tetrahydrobiopterin-dependent preservation of nitric oxide-mediated endothelial function in diabetes by targeted transgenic GTP-cyclohydrolase I overexpression.

Findings indicate that BH4 is an important mediator of eNOS regulation in diabetes and is a rational therapeutic target to restore NO-mediated endothelium-dependent vasodilatation in Diabetes and other vascular disease states.

Long-Term Vitamin C Treatment Increases Vascular Tetrahydrobiopterin Levels and Nitric Oxide Synthase Activity

Beneficial effect of vitamin C on vascular endothelial function appears to be mediated in part by protection of tetrahydrobiopterin and restoration of eNOS enzymatic activity, as measured in aortas of apoE-deficient mice.

Oxidation of the zinc-thiolate complex and uncoupling of endothelial nitric oxide synthase by peroxynitrite.

Evidence is presented of the first evidence that peroxynitrite (ONOO(-)) releases zinc from the zinc-thiolate cluster of endothelial NOS (eNOS) and presumably forms disulfide bonds between the monomers, providing a novel mechanism for modulation of the enzyme function in disease.

Redox control of endothelial function and dysfunction: molecular mechanisms and therapeutic opportunities.

The various ways in which ROS can influence endothelial function and dysfunction are outlined, the redox mechanisms involved are described, and approaches for preventing endothelial dysfunction are discussed that may highlight future therapeutic opportunities in the treatment of cardiovascular disease.

Coenzyme Q10 and diabetic endotheliopathy: oxidative stress and the 'recoupling hypothesis'.

  • G. ChewG. Watts
  • Biology, Chemistry
    QJM : monthly journal of the Association of Physicians
  • 2004
Coenzyme Q10 (CoQ), a potent antioxidant and a critical intermediate of the electron transport chain, may improve endothelial dysfunction by 'recoupling' eNOS and mitochondrial oxidative phosphorylation and act synergistically with anti-atherogenic agents, such as fibrates and statins to improve endotheliopathy in diabetes.
...

References

SHOWING 1-10 OF 51 REFERENCES

Tetrahydrobiopterin, nitric oxide and regulation of cerebral arterial tone

Effect of Vitamin C on the Availability of Tetrahydrobiopterin in Human Endothelial Cells

The results suggest that the beneficial effect of vitamin C on endothelial function is best explained by increased intracellular BH4 content and subsequent enhancement of eNOS activity, which appears to be independent of the ability ofitamin C to scavenge superoxide anions.

Tetrahydrobiopterin restores endothelial function in hypercholesterolemia.

Restoration of endothelial dysfunction by tetrahydrobiopterin suppletion in hypercholesterolemic patients is demonstrated and both the attenuated L-mono-methyl-arginine- induced vasoconstriction as well as the impaired serotonin-induced vasodilation were restored in patients during tetrahytochemical infusion.

Tetrahydrobiopterin and dysfunction of endothelial nitric oxide synthase in coronary arteries.

Hydrogen peroxide may be a mediator of endothelium-dependent relaxations in coronary arteries depleted of tetrahydrobiopterin and may represent an important mechanism underlying oxidative vascular injury.

Oxidation of tetrahydrobiopterin by peroxynitrite: implications for vascular endothelial function.

It is shown that abnormally low levels of BH(4) can promote a cycle of its own destruction mediated by nitric oxide synthase-dependent formation of peroxynitrite, which might contribute to vascular endothelial dysfunction induced by oxidative stress.

Endothelial Regulation of Vasomotion in ApoE-Deficient Mice: Implications for Interactions Between Peroxynitrite and Tetrahydrobiopterin

Reactive oxygen species may alter endothelium-dependent vascular relaxation not only by the interaction of O2·− with NO· but also through interactions between peroxynitrite and tetrahydrobiopterin.

Acute amelioration of diabetic endothelial dysfunction with a derivative of the nitric oxide synthase cofactor, tetrahydrobiopterin.

  • G. Pieper
  • Biology
    Journal of cardiovascular pharmacology
  • 1997
Tetrahydrobiopterin availability can play a key role in the regulation of nitric oxide production by diabetic endothelium and there was no effect of pteridine exposure on relaxation or sensitivity to nitroglycerin in diabetic rings (with or without endothelia) that are pretreated with L-nitroarginine.

Effect of tetrahydrobiopterin on endothelial function in canine middle cerebral arteries.

Increased availability of tetrahydrobiopterin may activate endothelial NO synthase in isolated canine middle cerebral arteries, and this effect appears to be critically dependent on the presence of superoxide dismutase.

Reactive Oxygen Species Mediate Endothelium-Dependent Relaxations in Tetrahydrobiopterin-Deficient Mice

It is demonstrated that H4B deficiency leads to eNOS dysfunction with the formation of reactive oxygen species, which become mediators of endothelium-dependent relaxations and thus contribute to the development of vascular diseases.

Oral Administration of Tetrahydrobiopterin Prevents Endothelial Dysfunction and Vascular Oxidative Stress in the Aortas of Insulin-Resistant Rats

Results indicate that BH4 augmentation is essential for the restoration of eNOS function and the reduction of vascular oxidative stress in insulin-resistant rats.
...