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The role of catalase and endothelium in hydrogen peroxide induced vasodilatation of human adipose arterioles.
Author(s) -
Wittenburg April L,
Phillips Shane A,
Gutterman David D
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.lb99
Background: Hydrogen peroxide (H 2 O 2 ) can serve as a key endothelial derived factor in regulating vascular tone and tissue blood flow, however the dose of exogenously added H 2 O 2 required for vasomotor responses is higher than expected from endogenous measured levels. We hypothesized that endogenous catalase, an H 2 O 2 scavenger, may explain the requirement for larger applied doses of H 2 O 2 to effect vasodilation. Methods: Arterioles (∼150 μm ID) obtained from patients without cardiovascular risk factors were cannulated and pressurized (60 mmHg) for videomicroscopy. After constriction with endothelin‐1, vasomotor responses to exogenous H 2 O 2 (10 −10 –10 −3 M) were evaluated in the presence and absence of the catalase inhibitor 3‐amino‐1,2,4‐triazole (ATZ) or after denudation. Results: Hydrogen peroxide dilated intact arterioles (ED 50 =2.98x10 −5 , n=15). Treatment with ATZ (4x10 −2 M) enhanced sensitivity to H 2 O 2 (ED 50 =2.44x10 −7 , n=7, P=0.0179). There was no effect of glutathione peroxidase inhibition with mercaptosuccinic acid (10 −2 M, ED 50 =6.11x10 −5 , n=2) alone or in combination with ATZ (ED 50 =1.05x10 −5 , n=4, P=ns) on H 2 O 2 induced vasodilation. Dilation to H 2 O 2 in denuded vessels was not significantly increased with ATZ (ED 50 =2.94x10 −5 , n=2). Conclusions: Endogenous catalase modulates H 2 O 2 signaling in an endothelium‐dependent manner, thus regulating vasodilation in the human microcirculation.