The Role of tetrahydrobiopterin and dihydrobiopterin in ischemia/reperfusion injury when given at reperfusion

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

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Reduced nitric oxide (NO) bioavailability and increased oxidative stress are major factors mediating ischemia/reperfusion (I/R) injury. Tetrahydrobiopterin (BH 4) is an essential cofactor of endothelial NO synthase (eNOS) to produce NO, whereas dihydrobiopterin (BH 2) can shift the eNOS product profile from NO to superoxide, which is further converted to hydrogen peroxide (H 2 O 2) and cause I/R injury. The effects of BH 4 and BH 2 on oxidative stress and postreperfused cardiac functions were examined in ex vivo myocardial and in vivo femoral I (20min)/R (45min) models. In femoral I/R, BH 4 increased NO and decreased H 2 O 2 releases relative to saline control, and these effects correlated with improved postreperfused cardiac function. By contrast, BH 2 decreased NO release relative to the saline control, but increased H 2 O 2 release similar to the saline control, and these effects correlated with compromised postreperfused cardiac function. In conclusion, these results suggest that promoting eNOS coupling to produce NO and decrease H 2 O 2 may be a key mechanism to restore postreperfused organ function during early reperfusion.

Original languageEnglish (US)
Article number963914
JournalAdvances in Pharmacological Sciences
Volume2010
DOIs
StatePublished - 2010

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