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Integration of dilator and constrictor pathways for arteriolar reactivity in the metabolic syndrome
Author(s) -
Frisbee Jefferson C.,
Brock Robert W.,
Hollander John M.
Publication year - 2009
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.23.1_supplement.948.10
Subject(s) - dilator , phenylephrine , adenosine , medicine , vasodilation , endocrinology , chemistry , acetylcholine , vasoconstriction , blood pressure
Previous study suggests that, with evolution of the metabolic syndrome, arteriolar reactivity is altered such that endothelium‐dependent dilation is attenuated and specific constrictor responses (adrenergic and myogenic) are enhanced, and may act to constrain hyperemia at low‐moderate metabolic demand. This study investigated interactions between dilator and constrictor reactivity in isolated resistance arterioles of obese Zucker rats (OZR). Dilation in OZR to acetylcholine, arachidonic acid (AA) and reduced PO2 was blunted vs. controls, although adenosine dilation was constrained only by structural alterations to the arteriolar wall. Increased adrenergic tone (phenylephrine) or intralumenal pressure (ILP) blunted dilation in both strains (OZR>LZR). Treatment of arterioles with TEMPOL (anti‐oxidant) or SQ‐29548 (PGH 2 /TxA 2 receptor antagonist) improved dilation to AA, hypoxia and acetylcholine with increased ILP, but had minimal effect with increased adrenergic tone. Adenosine dilation was maintained in both strains with increased ILP or adrenergic tone. These results suggest that constrictor effects of adrenergic tone and dilator influences of adenosine are robust contributors to integrated vascular tone, and that endothelium‐dependent stimuli and myogenic tone may act as modifiers via the impact of oxidant stress on NO availability and AA metabolism. (NIH R01 DK64668, AHA EIA 0740129N)