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Increased Cytochrome P450 2C9 signaling does not contribute to vascular endothelial dysfunction in healthy older adults
Author(s) -
Jablonski Kristen L,
Gano Lindsey B,
Lawson Brooke R,
Pierce Gary L,
Eskurza Iratxe,
Seals Douglas R,
Donato Anthony J
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.967.1
Subject(s) - medicine , vasodilation , sodium nitroprusside , brachial artery , endocrinology , oxidative stress , forearm , endothelium , dilator , plethysmograph , nitric oxide , surgery , blood pressure
Oxidative stress impairs endothelium‐dependent vasodilation (EDV) with aging in healthy sedentary adults. Increased cytochrome P450 2C9 (CYP450) signaling can contribute to oxidative stress‐mediated suppression of EDV, but its role in aging is unknown. We hypothesized that inhibition of CYP450 signaling with Sulfaphenazole (Sulfa) would improve EDV in older, but not young, healthy sedentary adults. At baseline, the increases in forearm blood flow (FBF; venous occlusion plethysmography) in response to incremental brachial artery infusions of acetylcholine (ACh; 1, 2, 4, and 8 μg 100mL forearm volume min −1 ), an endothelium‐dependent dilator, were smaller in older (n=16, 61±1 yr; mean±SE) vs. young (n=8; 22±1 yr) adults (P<0.05), with a reduction in peak FBF of 38% (10.4±0.97 vs.16.7±2.3 mL 100mL tissue −1 min −1 ). Co‐infusion of ACh with Sulfa at doses previously shown to block CYP450 signaling in humans did not significantly affect the FBF responses to ACh in either the older (peak FBF: 11.8±3.9 mL tissue −1 min −1 , P>0.05) or the young (peak FBF: 16.8±2.0 mL 100mL tissue −1 min −1 , P>0.05) group. Endothelium‐independent vasodilation, assessed with sodium nitroprusside, was similar in the young and older subjects and was not affected by Sulfa co‐infusion (P>0.05). These results indicate that increased CYP450 signaling does not contribute to impairments in EDV with aging in healthy adults.