Premium
Arginase inhibition increases the relaxation response to acetylcholine in murine mesenteric vessels
Author(s) -
Wynne Brandi M.,
Giachini Fernanda RC.,
SilvaSantos Jose Eduardo,
Tostes Rita C.,
Webb R. Clinton
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.1206.6
Subject(s) - arginase , acetylcholine , nitric oxide , phenylephrine , vascular smooth muscle , endocrinology , endothelial dysfunction , arginine , medicine , chemistry , nitric oxide synthase , mesenteric arteries , vasodilation , endothelium , ornithine , biochemistry , biology , smooth muscle , artery , blood pressure , amino acid
Endothelial dysfunction and smooth muscle hyper‐reactivity is characteristic of many vascular diseases. Arginase is a central enzyme in the urea cycle, hydrolyzing L‐arginine to urea and L‐ornithine. This process decreases arginine bioavailability for the production of nitric oxide (NO) by nitric oxide synthase (NOS). There is growing evidence that arginase plays a key role in vascular and endothelial dysfunction by decreasing NO production and uncoupling NOS leading to reactive oxygen species generation. Arginase expression and activity has also been shown to be increased in the large conductance vessels during hypertension. We tested the hypothesis that arginase inhibition in resistance arteries of the mesentery would enhance endothelium‐mediated relaxation. C57Bl6 mice were killed; 1 st order mesenteric vessels were isolated and then subjected to standard muscle bath procedure. Concentration response curves (CRC) to phenylephrine and acetylcholine were performed with or without the arginase inhibitor, nor‐NOHA [3×10 −4 M]. Vessels incubated with nor‐NOHA exhibited a leftward shift in the CRC to acetylcholine (p<0.005). These data suggest that arginase acts to limit the pool of arginine available for relaxation to acetylcholine in resistance arteries in mice. This work is funded by NIH HL074167.