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The complex role of hydrogen peroxide (H2O2) in acetylcholine‐induced dilation of human mucosal intestinal microvessels
Author(s) -
Hatoum Ossama A.,
Binion David G.,
Miura Hiroto,
Larsen Brandon T.,
Selle Rebecca M.,
Kopelman Doron,
Gutterman David D.
Publication year - 2006
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.20.4.a282-d
Subject(s) - constriction , vasoconstriction , acetylcholine , vasodilation , endothelium , chemistry , nitric oxide , thromboxane a2 , cyclooxygenase , microcirculation , pharmacology , endocrinology , anesthesia , medicine , biochemistry , receptor , enzyme
We previously reported that normal mucosal intestinal microvessels dilate in an endothelium‐dependent manner to acetylcholine (Ach) with nitric oxide and cyclooxygenase products contributing approximately 80% of the dilation. Catalase, a selective H 2 O 2 dismutase abolished the remaining dilation revealing vasoconstriction similar to endothelial denudation suggesting that H 2 O 2 might be an EDHF. In the present study we determined the mechanism of H 2 O 2 ‐mediated constriction in mucosal arterioles. Arterioles (160 ± 24 μm) were dissected from normal gut specimens, cannulated and pressurized at 60 mmHg. Changes in the diameter were recorded using videomicroscopy. Exogenous H 2 O 2 dilated microvessels in a concentration‐dependent fashion (max dilation (MD) 52% + 10%, n = 7). Endothelial denudation using luminal air infusion resulted in a concentration‐dependent vasoconstriction (MD; −51% + 6%, n = 6) indicating that H 2 O 2 is not the EDHF. Both the thromboxane A 2 receptor block SQ‐29548 and the non‐selective cyclooxygenase inhibitor indomethacin converted the constriction into dilation (MD; 42% + 16%, 85% + 7%, respectively) in denuded arterioles. SQ‐29548 augmented dilation in intact microvessels (MD; 93% + 3%, p<0.05 vs. control). These data provide evidence that the endothelium plays a critical role in the response to H 2 O 2 which is not an EDHF in the mucosal gut vasculature. H 2 O 2 acts through the endothelium and vascular smooth muscle to elicit dilation and constriction simultaneously. Our data suggest an important role of thromboxane in the constriction to H 2 O 2