Document Detail

Local ascorbate administration augments NO- and non-NO-dependent reflex cutaneous vasodilation in hypertensive humans.
MedLine Citation:
PMID:  17483240     Owner:  NLM     Status:  MEDLINE    
Full expression of reflex cutaneous vasodilation (VD) is dependent on nitric oxide (NO) and is attenuated with essential hypertension. Decreased NO-dependent VD may be due to 1) increased oxidant stress and/or 2) decreased L-arginine availability through upregulated arginase activity, potentially leading to increased superoxide production through uncoupled NO synthase (NOS). The purpose of this study was to determine the effect of antioxidant supplementation (alone and combined with arginase inhibition) on attenuated NO-dependent reflex cutaneous VD in hypertensive subjects. Nine unmedicated hypertensive [HT; mean arterial pressure (MAP) = 112 +/- 1 mmHg] and nine age-matched normotensive (NT; MAP = 81 +/- 10 mmHg) men and women were instrumented with four intradermal microdialysis (MD) fibers: control (Ringer), NOS inhibited (NOS-I; 10 mM N(G)-nitro-L-arginine), L-ascorbate supplemented (Asc; 10 mM L-ascorbate), and Asc + arginase inhibited [Asc+A-I; 10 mM L-ascorbate + 5 mM (S)-(2-boronoethyl)-L-cysteine-HCl + 5 mM N(omega)-hydroxy-nor-L-arginine]. Oral temperature was increased by 0.8 degrees C via a water-perfused suit. N(G)-nitro-L-arginine was then ultimately perfused through all MD sites to quantify the change in VD due to NO. Red blood cell flux was measured by laser-Doppler flowmetry over each skin MD site, and cutaneous vascular conductance (CVC) was calculated (CVC = flux/MAP) and normalized to maximal CVC (%CVC(max); 28 mM sodium nitroprusside + local heating to 43 degrees C). During the plateau in skin blood flow (Delta T(or) = 0.8 degrees C), cutaneous VD was attenuated in HT skin (NT: 42 +/- 4, HT: 35 +/- 3 %CVC(max); P < 0.05). Asc and Asc+A-I augmented cutaneous VD in HT (Asc: 57 +/- 5, Asc+A-I: 53 +/- 6 %CVC(max); P < 0.05 vs. control) but not in NT. %CVC(max) after NOS-I in the Asc- and Asc+A-I-treated sites was increased in HT (Asc: 41 +/- 4, Asc+A-I: 40 +/- 4, control: 29 +/- 4; P < 0.05). Compared with the control site, the change in %CVC(max) within each site after NOS-I was greater in HT (Asc: -19 +/- 4, Asc+A-I: -17 +/- 4, control: -9 +/- 2; P < 0.05) than in NT. Antioxidant supplementation alone or combined with arginase inhibition augments attenuated reflex cutaneous VD in hypertensive skin through NO- and non-NO-dependent mechanisms.
Lacy A Holowatz; W Larry Kenney
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-05-04
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  293     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-08-03     Completed Date:  2007-09-18     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1090-6     Citation Subset:  IM    
Noll Laboratory, The Pennsylvania State University, Univerisity Park, PA 16802, USA.
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MeSH Terms
Administration, Cutaneous
Antioxidants / administration & dosage*
Arginase / antagonists & inhibitors,  metabolism*
Ascorbic Acid / administration & dosage*
Blood Flow Velocity / drug effects
Blood Vessels / drug effects,  innervation,  metabolism
Boronic Acids / administration & dosage
Case-Control Studies
Enzyme Inhibitors / administration & dosage
Fever / metabolism,  physiopathology
Hypertension / enzymology,  metabolism*,  physiopathology
Laser-Doppler Flowmetry
Middle Aged
NG-Nitroarginine Methyl Ester / administration & dosage
Nitric Oxide / metabolism*
Nitric Oxide Synthase / antagonists & inhibitors,  metabolism
Reflex / drug effects*
Skin / blood supply*
Time Factors
Vasodilation / drug effects*
Grant Support
M01 RR10732/RR/NCRR NIH HHS; R01 AG07004-17/AG/NIA NIH HHS
Reg. No./Substance:
0/(2-boronoethyl)-cysteine; 0/Antioxidants; 0/Boronic Acids; 0/Enzyme Inhibitors; 10102-43-9/Nitric Oxide; 50-81-7/Ascorbic Acid; 50903-99-6/NG-Nitroarginine Methyl Ester; EC Oxide Synthase; EC

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