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Tetrahydrobiopterin (BH4) attenuates neutrophil adhesion/transmigration in myocardial ischemia/reperfusion injury
Author(s) -
Elio Katrina,
Kim Elizabeth Eun Jung,
Chen Qian,
Kay Helen Y,
Adams Jovan,
Young Lindon Howard
Publication year - 2007
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.21.6.a1145-c
Subject(s) - tetrahydrobiopterin , nitric oxide , endothelial dysfunction , medicine , ischemia , infiltration (hvac) , endothelium , reperfusion injury , icam 1 , nitric oxide synthase , cardiac function curve , cardiology , endocrinology , cell adhesion molecule , pharmacology , chemistry , immunology , heart failure , physics , thermodynamics
Attenuating endothelial dysfunction during early reperfusion (i.e., within the first 5 min) inhibits upregulation of endothelial adhesion molecules, attenuates PMN‐endothelium interaction, and restores post‐reperfusion cardiac contractile function. BH 4 is an essential cofactor of endothelial nitric oxide synthase to produce nitric oxide. We hypothesize that BH 4 , not dihydrobiopterin (BH 2 , i.e., oxidized BH 4 ), given during reperfusion will attenuate PMN vascular adherence and infiltration and restore cardiac function in isolated rat hearts subjected to ischemia (20 min) and reperfusion (45 min)and reperfused with PMNs. In BH 4 treated I/R+PMN hearts (10uM, n=6), left ventricular developed pressure (LVDP) at 45 min post reperfusion significantly recovered to 85±8% of baseline, whereas I/R+PMN hearts and BH 2 ‐perfused hearts only recovered to 53±7% and 64±9% of baseline (P<0.01). IR/PMN perfused BH 4 hearts were associated with decreased PMN coronary vascular adherence, tissue infiltration, and attenuated ICAM‐1 expression, compared to IR/PMN hearts or BH 2 ‐perfused hearts. This preliminary data suggest that BH 4 attenuates PMN induced post‐I/R LVDP dysfunction, in part, by attenuating PMN vascular adherence and tissue infiltration, possibly by inhibiting ICAM‐1 expression. This study was supported by NHLBI Grant 1R15HL‐76235‐01 and Center For Chronic Disorders Of Aging. Philadelphia College of Osteopathic Medicine.