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Aging and high intravascular pressure increase eNOS uncoupling
Author(s) -
Yang YangMing,
Huang An,
Kaley Gabor,
Sun Dong
Publication year - 2008
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.22.1_supplement.1119.9
Subject(s) - enos , endocrinology , medicine , superoxide , mesenteric arteries , apocynin , chemistry , nadph oxidase , nitric oxide , nitric oxide synthase , oxidative stress , biochemistry , artery , enzyme
eNOS uncoupling is an important mechanism that leads to endothelial dysfunction. Previously, we reported that shear stress‐induced release of NO in vessels of aged rats was significantly reduced, which was accompanied by increased production of superoxide. Furthermore, we found that in aged vessels superoxide production induced by high intravascular pressure was reduced by inhibition of NO synthase. In the present study, we investigated the influence of aging on eNOS uncoupling. Mesenteric arteries were isolated from young (3 month) and aged (24 month) C57 BL/6J mice. The expression of eNOS protein in young vs. aged mice was not significantly different. However, when we determined the ratio of eNOS monomers vs. dimers in young and aged mice, the aged mice had a significant increase in the monomer component. When isolated and perfused mesenteric arteries (∼200 μm) from aged mice were exposed to high intravascular pressure (180 mmHg) for 1 h, the ratio of eNOS monomers in these vessels was further elevated, and the elevation remained constant for 4 h. Interestingly, inhibition of NAD(P)H oxidase with apocynin (100 μM) protected the vessels from an increase in eNOS monomers. These data suggest that superoxide production may affect eNOS uncoupling, which could contribute to endothelial dysfunction in aged vessels. (Supported by NIH HL‐43023, HL‐68813 and HL‐070653)