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NADPH Plays a Critical Role in Modulating Endothelial Dysfunction in the Post‐Ischemic Heart.
Author(s) -
Reyes Levy A,
Dumitrescu Cristian,
Druhan Lawrence J,
Talukder M. A. Hassan,
Zweier Jay L
Publication year - 2009
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.23.1_supplement.793.22
Subject(s) - enos , endothelial dysfunction , ischemia , nitric oxide , medicine , endothelial nitric oxide synthase , cardiology , endothelium , nitric oxide synthase
Reperfusion injury has been shown to cause dysfunction in vascular endothelium. The current understanding of this relationship is incomplete, but is critical in developing new treatments of post‐ischemic myocardium. Previously we demonstrated that endothelial dysfunction does not involve a loss of endothelial nitric oxide synthase (eNOS), but rather is triggered by loss of cofactors/substrates of the enzyme. Recently we showed the eNOS cofactor, BH 4 , to be depleted in the ischemic heart, and restoration of lost BH 4 in isolated heart preparations partially rescued coronary flow. Our current work extends these studies to NADPH, an eNOS substrate. We have found that NADPH declines to ~30% of normal levels at 30 minutes post‐ischemia. The importance of this decline in the eNOS substrate was shown in isolated hearts, where repletion of lost NADPH 30 minutes post ischemia resulted in a dramatic improvement in coronary flow, increasing 77 ± 4% of control. It remains to be determined why the decrease in NADPH occurs, and if this loss can be prevented during ischemia/reperfusion injury. In spite of these questions repletion of eNOS cofactors/substrates may be an efficacious therapy for improving endothelial dysfunction in the post‐ischemic heart.