The Role of Tetrahydrobiopterin and Dihydrobiopterin in Ischemia/Reperfusion Injury when Given at Reperfusion
This article was published in Advances in Pharmacological Sciences, Volume 2010, Article ID 963914, 11 pages
The published version is available at http://dx.doi.org/10.1155/2010/963914
Copyright © 2010 Qian Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 (20 min)/R (45 min) 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.