TY - JOUR
T1 - The Role of Tetrahydrobiopterin and Dihydrobiopterin in Ischemia/Reperfusion Injury When Given at Reperfusion
AU - Chen, Qian
AU - Kim, Elizabeth Eun Jung
AU - Elio, Katrina
AU - Zambrano, Christopher
AU - Krass, Samuel
AU - Teng, Jane Chun-Wen
AU - Kay, Helen
AU - Perkins, Kerry-Anne
AU - Pershad, Sailesh
AU - McGraw, Sloane
AU - Emrich, Jeffrey
AU - Adams, Jovan S.
AU - Young, Lindon H.
PY - 2010/1/1
Y1 - 2010/1/1
N2 - 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.
AB - 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.
UR - https://digitalcommons.pcom.edu/scholarly_papers/51
M3 - Article
VL - 2010
JO - Advances in Pharmacological Sciences
JF - Advances in Pharmacological Sciences
ER -