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The in vivo role of arginase in cutaneous microvascular dysfunction in hypercholesterolemic humans before and after statin therapy
Author(s) -
Holowatz Lacy A.,
Lang James A.,
Sorkin Jeremy J.,
Kenney W. Larry
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.777.5
Subject(s) - arginase , vasodilation , atorvastatin , medicine , microdialysis , endocrinology , in vivo , statin , nitric oxide , enos , chemistry , arginine , nitric oxide synthase , biochemistry , biology , microbiology and biotechnology , amino acid , central nervous system
Elevated low‐density lipoproteins (LDL) are associated with systemic vascular dysfunction evident in the cutaneous microvasculature. Our aim was to determine the role of arginase and freely exchangeable L‐arginine (L‐arg) in vivo in reduced NO‐dependent vasodilation (VD) in hypercholesteroleΔic (HC) skin before and after statin therapy. Three intradermal microdialysis (MD) fibers were placed in 5 normocholesterolemic (NC) (LDL=92 ±8 mg/dl) and 6 HC subjects before (LDL=179±6 mg/dl) and after 3 months of atorvastatin (10 mg) (LDL=100±7 mg/dl): control, arginase‐inhibited (A‐I: 5 mM BEC), and L‐arg (10 mM). Skin blood flow (SkBF) was measured while local skin heating (42°C) induced NO‐dependent VD [quantified (ΔNO) by infusing 10 mM L‐NAME after the plateau (P) in SkBF]. Cutaneous vascular conductance (CVC= flux/MAP) was normalized to max (50 mM SNP). VD was reduced in HC (HC: 77±5 vs. NC: 94±5 % max, p<0.05) as was ΔNO (HC: 37±5 vs. NC: 61±6 % max, p<0.05). P and ΔNO were augmented in HC with A‐I (P: 92±3, ΔNO: 65±3% max, p<0.05) and L‐arg (P: 95±3, ΔNO: 75±4% max, p<0.05) but not in NC. After statin therapy there was no difference between control (P: 92±2, ΔNO: 51±4% max) and A‐I (P: 97±1, ΔNO: 62±6% max, p>0.05) or L‐arg (P: 94±3, ΔNO: 56±5% max, p>0.05) sites. Reduced NOS substrate availability through upregulated arginase contributes to cutaneous microvascular dysfunction with HC, which is corrected with statin therapy.