ArticleAmerican journal of physiology. Heart and circulatory physiology2009
Role of tetrahydrobiopterin in resistance to myocardial ischemia in Brown Norway and Dahl S rats.
Article in American journal of physiology. Heart and circulatory physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Tetrahydrobiopterin prevents chronic ischemia-related lower urinary tract dysfunction through the maintenance of nitric oxide bioavailability.Scientific reports · 2020Article
- Cardiomyocyte GTP Cyclohydrolase 1 Protects the Heart Against Diabetic Cardiomyopathy.Scientific reports · 2016Article
- Isoflurane favorably modulates guanosine triphosphate cyclohydrolase-1 and endothelial nitric oxide synthase during myocardial ischemia and reperfusion injury in rats.Anesthesiology · 2015Article
- Netrin-1 abrogates ischemia/reperfusion-induced cardiac mitochondrial dysfunction via nitric oxide-dependent attenuation of NOX4 activation and recoupling of NOS.Journal of molecular and cellular cardiology · 2015Article
- Enoyl coenzyme a hydratase domain-containing 2, a potential novel regulator of myocardial ischemia injury.Journal of the American Heart Association · 2013Article
- Differential sensitivity to LPS-induced myocardial dysfunction in the isolated brown Norway and Dahl S rat hearts: roles of mitochondrial function, NF-κB activation, and TNF-α production.Shock (Augusta, Ga.) · 2012Article
- The protein partners of GTP cyclohydrolase I in rat organs.PloS one · 2012Article
- Two-marker association tests yield new disease associations for coronary artery disease and hypertension.Human genetics · 2011Article
- Modeling of biopterin-dependent pathways of eNOS for nitric oxide and superoxide production.Free radical biology & medicine · 2011Article
- Tetrahydrobiopterin restores diastolic function and attenuates superoxide production in ovariectomized mRen2.Lewis rats.Endocrinology · 2011Article
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
Abstract
Previously we showed that Brown Norway (BN/Mcw) rats are more resistant to myocardial ischemia-reperfusion (I/R) injury than Dahl S (SS/Mcw) rats due to increased nitric oxide (x NO) generation secondary to increased heat shock protein 90 (HSP90) association with endothelial nitric oxide synthase (NOS3). Here we determined whether increased resistance to I/R injury in BN/Mcw hearts is also related to tetrahydrobiopterin (BH(4)) and GTP cyclohydrolase I (GCH-1), the rate-limiting enzyme for BH(4) synthesis. We observed that BH(4) supplementation via sepiapterin (SP) and inhibition of GCH-1 via 2,4-diamino-6-hydroxypyrimidine (DAHP) differentially modulate cardioprotection and that SP alters the association of HSP90 with NOS3. BH(4) levels were significantly higher and 7,8-dihydrobiopterin (BH(2)) levels were significantly lower in BN/Mcw than in SS/Mcw hearts. The BH(4)-to-BH(2) ratio in BN/Mcw was more than two times that in SS/Mcw hearts. After I/R, BH(4) decreased and BH(2) increased in hearts from both strains compared with their preischemia levels. However, the increase in BH(2) in SS/Mcw hearts was significantly higher than in BN/Mcw hearts. Real-time PCR revealed that BN/Mcw hearts contained more GCH-1 transcripts than SS/Mcw hearts. SP increased recovery of left ventricular developed pressure (rLVDP) following I/R as well as decreased superoxide (O(2)(x-)) and increased x NO in SS/Mcw hearts but not in BN/Mcw hearts. DAHP decreased rLVDP as well as increased O(2)(x-) and decreased x NO in BN/Mcw hearts compared with controls but not in SS/Mcw hearts. SP increased the association of HSP90 with NOS3. These data indicate that BH(4) mediates resistance to I/R by acting as a cofactor and enhancing HSP90-NOS3 association.
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