The Role of Tetrahydrobiopterin and Dihydrobiopterin in Ischemia/Reperfusion Injury When Given at Reperfusion

Chen, Qian; Kim, Elizabeth Eun Jung; Elio, Katrina; Zambrano, Christopher; Krass, Samuel; Teng, Jane; Kay, Helen; Perkins, Kerry-Anne; Pershad, Sailesh; McGraw, Sloane; Emrich, Jeffrey; Adams, Jovan; Young, Lindon H.

doi:10.1155/2010/963914

Cited by 14 publications

(33 citation statements)

References 24 publications

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“…After hindlimb ischemia in rabbits, Huk et al (17) showed increases in NO release in femoral artery smooth muscle during reperfusion in the range of 100 -200 nM in quercetin-treated group. These are similar to our own observations in rats measuring the effect of test compounds designed to improve NO release derived from eNOS (10). These measurements have helped to confirm that increased NO release during reperfusion attenuates reperfusion-associated inflammation (17 (19) found micromolar increases in gastric NO release after ingestion of nitrate-supplemented water.…”

Section: In Vivo Applicationssupporting

confidence: 86%

“…This group also validated the real-time NO measurement by comparison with the Greiss reaction, which showed an increase in serum nitrite/nitrate levels after acetylcholine administration. The human intravascular responses are similar to the range detected in our rat femoral I/R model, using a 100 µm diameter sensor (10).…”

Section: In Vivo Applicationssupporting

confidence: 71%

“…In practice, some NO is immediately oxidized to nitrite and not detected by the sensor. Furthermore, SNAP decomposition does not go to completion even in the presence of a catalyst [10]. Consequently, the detected NO is about 60% of the SNAP concentration.…”

Section: In Vivo Methodsmentioning

confidence: 96%

“…by superoxide dismutase. Therefore, eNOS can become a source of oxidative stress during endothelial dysfunction (10,11). These are the first events of an inflammatory response, which, even if checked, may result in permanent organ damage (7,12,13).…”

Section: Endothelial Dysfunctionmentioning

confidence: 99%

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Direct Measurement of Hydrogen Peroxide (H2O2) or Nitric Oxide (NO) Release: A Powerful Tool to Assess Real-time Free Radical Production in Biological Models

Young

Chen²,

Weis³

2011

Am. J. Biomed. Sci.

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Vascular endothelial dysfunction is a common and early event occurring in many disease conditions, such as ischemia/reperfusion (I/R) injury, vascular complications of diabetes, and clinical procedures that injure blood vessels. The hallmark of endothelial dysfunction is reduced bioavailability of nitric oxide (NO) and consequent increased free radical production. These radicals trigger the inflammatory response, a major contributor to tissue injury. Measuring free radical release in biological models facilitates assessment of the biochemical mechanisms responsible for regulating the production of these biomolecules. This technical review focuses on the application of real-time measurement of hydrogen peroxide (H 2 O 2 ) and NO release in models of I/R and blood vessel injury. The technique presents a valuable tool to study not only NO/H 2 O 2 release, but also to identify novel pharmacologic agents modifying that release.

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Section: In Vivo Applicationssupporting

confidence: 86%

Section: In Vivo Applicationssupporting

confidence: 71%

Section: In Vivo Methodsmentioning

confidence: 96%

Section: Endothelial Dysfunctionmentioning

confidence: 99%

See 2 more Smart Citations

Direct Measurement of Hydrogen Peroxide (H2O2) or Nitric Oxide (NO) Release: A Powerful Tool to Assess Real-time Free Radical Production in Biological Models

Young

Chen²,

Weis³

2011

Am. J. Biomed. Sci.

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“…Both femoral arteries and veins were exteriorized and NO microsensors (100 μm, World Precision Instruments (WPI) Inc., Sarasota, FL) were inserted into both femoral veins via 24 gauge catheters as previously described [37,38]. Following a 15-minute baseline measurement, one femoral artery/vein was clamped for 20 minutes while the contralateral limb served as the sham control.…”

Section: Global Cardiac Ischemiamentioning

confidence: 99%

Triacsin C, a Fatty Acyl CoA Synthetase Inhibitor, Improves Cardiac Performance Following Global Ischemia

Blakeman¹,

Chen²,

Tolson³

et al. 2012

Am. J. Biomed. Sci.

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The role of fatty acyl CoA synthetase (FACS) in ischemia/reperfusion (I/R) injury has not been well established. Our earlier studies showed that triacsin C, a selective FACS inhibitor, decreases endothelial nitric oxide synthase (eNOS) palmitoylation and increases nitric oxide (NO) in cultured human coronary endothelial cells. In the present study, we tested the hypothesis that triacsin C would reduce infarct size and improve post-reperfusion cardiac function by increasing vascular NO. In isolated rat hearts, triacsin C, given during the first 5 minutes of reperfusion, significantly reduced infarct size and attenuated cardiac dysfunction during reperfusion. N G -nitro-L-arginine methyl ester (L-NAME, a non-selective NOS inhibitor, 50 µM) completely abolished the protective effects of triacsin C. In the ischemic hind limb model, triacsin C significantly increased intravascular NO concentration during reperfusion, an effect that was blocked by L-NAME or S-methyl-L-thiocitrulline (SMTC, a selective neuronal NOS inhibitor), but not by 1400W (a highly selective iNOS inhibitor). Lastly, triacsin C significantly reduced L-NAME induced leukocyte rolling, adhesion, and transmigration in rat mesenteric circulation, as measured by intravital microscopy. In summary, this study provides novel evidence showing that triacsin C reduces myocardial infarct size, attenuates loss of post-reperfusion cardiac function, increases intravascular NO concentration and inhibits leukocyte recruitment. These pharmacologic properties suggest that triacsin C may be useful as an adjunct to Am.

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The effects of modulating eNOS activity and coupling in ischemia/reperfusion (I/R)

Perkins

Pershad

Chen

et al. 2011

Naunyn-Schmiedeberg's Arch Pharmacol

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The in vivo role of endothelial nitric oxide synthase (eNOS) uncoupling mediating oxidative stress in ischemia/reperfusion (I/R) injury has not been well established. In vitro, eNOS coupling refers to the reduction of molecular oxygen to L-arginine oxidation and generation of L-citrulline and nitric oxide NO synthesis in the presence of an essential cofactor, tetrahydrobiopterin (BH(4)). Whereas uncoupled eNOS refers to that the electron transfer becomes uncoupled to L-arginine oxidation and superoxide is generated when the dihydrobiopterin (BH(2)) to BH(4) ratio is increased. Superoxide is subsequently converted to hydrogen peroxide (H(2)O(2)). We tested the hypothesis that promoting eNOS coupling or attenuating uncoupling after I/R would decrease H(2)O(2)/increase NO release in blood and restore postreperfused cardiac function. We combined BH(4) or BH(2) with eNOS activity enhancer, protein kinase C epsilon (PKC ε) activator, or eNOS activity reducer, PKC ε inhibitor, in isolated rat hearts (ex vivo) and femoral arteries/veins (in vivo) subjected to I(20 min)/R(45 min). When given during reperfusion, PKC ε activator combined with BH(4), not BH(2), significantly restored postreperfused cardiac function and decreased leukocyte infiltration (p < 0.01) while increasing NO (p < 0.05) and reducing H(2)O(2) (p < 0.01) release in femoral I/R veins. These results provide indirect evidence suggesting that PKC ε activator combined with BH(4) enhances coupled eNOS activity, whereas it enhanced uncoupled eNOS activity when combined with BH(2). By contrast, the cardioprotective and anti-oxidative effects of the PKC ε inhibitor were unaffected by BH(4) or BH(2) suggesting that inhibition of eNOS uncoupling during reperfusion following sustained ischemia may be an important mechanism.

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The Role of Tetrahydrobiopterin and Dihydrobiopterin in Ischemia/Reperfusion Injury When Given at Reperfusion

Cited by 14 publications

References 24 publications

Direct Measurement of Hydrogen Peroxide (H2O2) or Nitric Oxide (NO) Release: A Powerful Tool to Assess Real-time Free Radical Production in Biological Models

Direct Measurement of Hydrogen Peroxide (H2O2) or Nitric Oxide (NO) Release: A Powerful Tool to Assess Real-time Free Radical Production in Biological Models

Triacsin C, a Fatty Acyl CoA Synthetase Inhibitor, Improves Cardiac Performance Following Global Ischemia

The effects of modulating eNOS activity and coupling in ischemia/reperfusion (I/R)

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