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Mechanisms of hydrogen peroxide induced vasoconstriction in human adipose resistance arteries
Author(s) -
Phillips Shane A.,
Somberg Lewis B.,
Hatoum O A,
Gutterman David D.
Publication year - 2007
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.21.5.a491-c
Subject(s) - dilator , vasodilation , vasoconstriction , vasomotor , medicine , vascular resistance , endothelium , endocrinology , microcirculation , arachidonic acid , pharmacology , chemistry , hemodynamics , biochemistry , enzyme
Previous studies indicate that hydrogen peroxide (H 2 O 2 ) is an important regulator of vascular tone and blood flow during pathophysiological conditions, with responses ranging from dilation to constriction. The purpose of this study was to determine the mechanism of H 2 O 2 ‐ induced vasomotor responses in the human microcirculation using omental arterioles from patients without cardiovascular disease or risk factors. Arteries (~150 μm) obtained at surgery from patients were cannulated and pressurized (60 mmHg) for videomicroscopy. Vasomotor responses to exogenous H 2 O 2 (10 −7 to 10 −3 M) were evaluated in the presence and absence of an intact endothelium. H 2 O 2 dilated intact arterioles [%MD: 90±1.5%]. Blockade of NOS with L‐NAME (10 −4 M), L‐NAME and indomethacin (INDO; 10 −5 M), or the TXA 2 /PGH 2 receptor antagonist (SQ‐29548; 10 −5 M) had no effect on H 2 O 2 ‐ induced vasodilation. However, dilation to H 2 O 2 was reduced with 17‐ODYA (10 −5 M) or 30 mM KCl. Endothelium removal caused H 2 O 2 induced constriction that was eliminated by INDO and reversed to dilation by SQ‐29548. Vasodilation to H 2 O 2 in the presence of SQ‐29548 was eliminated by PGD 2 receptor antagonism BW A868C (10 −6 M). These data suggest that dilation to H 2 O 2 depend on cytochrome P450 metabolites of arachidonic acid in resistance arteries and that H 2 O 2 ‐ induced constrictor responses are mediated by smooth muscle TXA 2 generation in the absence of endothelium. This study provides initial evidence for a complex interplay between H 2 O 2 ‐derived endothelial dilator and smooth muscle constrictor metabolites of arachidonic acid in human resistance arteries.