Premium
Ischemia‐Reperfusion Injury Targets Endothelial Specific NADPH, Resulting in Endothelial Dysfunction in the Isolated Heart
Author(s) -
Reyes Levy Austin,
Dumitrescu Cristian,
Wang TseYao,
Druhan Lawrence,
Zweier Jay Louis
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.643.24
Ischemia‐Reperfusion (IR) injury is a well documented phenomenon brought about through therapeutic intervention for ischemic heart disease, and has been shown to cause vascular dysfunction; the current understanding of which is incomplete. Previously, we reported in isolated hearts the level of the eNOS substrate, NADPH, is depleted after 30 min of IR injury, furthermore, restoration of this lost NADPH resulted in a dramatic recovery of coronary flow. Coronary recovery with NADPH is L‐NAME inhibitable and almost four times above current published recovery with Tetrahydrobiopterin (BH 4 ) supplementation. Interestingly, while our previous studies reported a decrease of NADPH in whole heart homogenates, these levels remained well above the kM for eNOS activity (2.6 μM), and raised questions as to how repletion of the eNOS substrate exhibited such a robust physiological response. To better understand this phenomenon we infused 0.25% Triton to isolated hearts receiving no injury or 30 min of IR injury. HPLC analysis for NADP(H) was performed on the effluent of these hearts. Levels of NADP(H) in non‐injured hearts were nearly undetectable (1.00 ± 0.45 μM/ml of effluent * min) and dramatically lower when compared to non‐injured hearts (4.25 ± 1.77 μM/ml of effluent*min). Therefore, while IR injury affects whole heart levels of NADPH with a decline of ~47%; this decline is more dramatic in the endothelium, ~76%.