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Cited by 189

The DOI matches its OpenAlex record; 3 of the 3 references it cites were found in a registry or an index.

Impaired nitric oxide production in coronary endothelial cells of the spontaneously diabetic BB rat is due to tetrahydrobiopterin deficiency

Open access
Cynthia J. Meininger, Rebecca S. MARINOS, Kazuyuki Hatakeyama, Raul Martı́nez–Zaguilán, José D. Rojas, Katherine A. Kelly, Guoyao Wu·2000·Biochemical Journal

Abstract

Endothelial cells (EC) from diabetic BioBreeding (BB) rats have an impaired ability to produce NO. This deficiency is not due to a defect in the constitutive isoform of NO synthase in EC (ecNOS) or alterations in intracellular calcium, calmodulin, NADPH or arginine levels. Instead, ecNOS cannot produce sufficient NO because of a deficiency in tetrahydrobiopterin (BH(4)), a cofactor necessary for enzyme activity. EC from diabetic rats exhibited only 12% of the BH(4) levels found in EC from normal animals or diabetes-prone animals which did not develop disease. As a result, NO synthesis by EC of diabetic rats was only 18% of that for normal animals. Increasing BH(4) levels with sepiapterin increased NO production, suggesting that BH(4) deficiency is a metabolic basis for impaired endothelial NO synthesis in diabetic BB rats. This deficiency is due to decreased activity of GTP-cyclohydrolase I, the first and rate-limiting enzyme in the de novo biosynthesis of BH(4). GTP-cyclohydrolase activity was low because of a decreased expression of the protein in the diabetic cells.

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OpenAlex · 10.1042/0264-6021:3490353

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Metadata

Authors
Meininger, C. J., MARINOS, R. S., Hatakeyama, K., Martı́nez–Zaguilán, R., Rojas, J. D., Kelly, K. A., & Wu, G.
Venue
Biochemical Journal
Publisher
Portland Press
Published
2000-06-26
Volume
349
Issue
1
Pages
353-353
ISSN
0264-6021 (ISSN-L)
OpenAlex
W2048574237
Cited by
189
References
3
FWCI
6.80
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Impaired nitric oxide production in coronary endothelial cells of the spontaneously diabetic BB rat is due to tetrahydrobiopterin deficiency. https://app.cochat.ai/papers/10.1042/0264-6021:3490353
The paper
Meininger, C. J., MARINOS, R. S., Hatakeyama, K., Martı́nez–Zaguilán, R., Rojas, J. D., Kelly, K. A., & Wu, G. (2000). Impaired nitric oxide production in coronary endothelial cells of the spontaneously diabetic BB rat is due to tetrahydrobiopterin deficiency. Biochemical Journal. https://doi.org/10.1042/0264-6021%3A3490353

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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