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Acute glutathione supplementation enhances endothelial‐mediated coronary artery dilation
Author(s) -
Levy Andrew S,
Smith Christopher S,
Rush James WE
Publication year - 2010
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.24.1_supplement.1034.2
Subject(s) - glutathione , bradykinin , nitric oxide , vasodilation , chemistry , pharmacology , antioxidant , medicine , sodium nitroprusside , cardiology , endocrinology , biochemistry , receptor , enzyme
Reports from both human and animal studies demonstrate that acute thiol manipulation influences both vascular function and nitric oxide (NO) production. To this end acute glutathione (GSH) administration has been used to enhance coronary vasodilation; however, the mechanisms have not been fully resolved. The purpose of this investigation was to determine how acute GSH administration alters NO‐mediated coronary artery dilation. Endothelial function was assessed in isolated, perfused hearts using a Langendorff apparatus. GSH was administered at concentrations of 0 (CON), 1 or 10 μM and dose‐response curves to bradykinin (BK) were constructed. The sensitivity to BK was enhanced at the 10 μM concentration (p<0.01) and no differences were seen in maximal dilation. In the presence of LNAME (0.1 mM) and/or sGC inhibition (ODQ, 3 μM) the sensitivity to BK remained enhanced in the presence of GSH (10 μM) (p<0.05). Treatment with TEMPOL (0.1 mM) enhanced the sensitivity to BK in CON similar to the effect of GSH (10 μM) and GSH (10 μM)+TEMPOL (0.1 mM). TEMPOL enhanced the sensitivity to exogenous NO (SNP), whereas GSH slightly reduced maximal dilation to SNP. Collectively, these results suggest GSH enhances BK mediated dilation through an antioxidant‐dependent mechanism unrelated to NO production or utilization. Supported by Heart and Stroke Foundation & Natural Science and Engineering Research Council