Document Detail

Upregulation of inducible nitric oxide synthase contributes to attenuated cutaneous vasodilation in essential hypertensive humans.
MedLine Citation:
PMID:  21931069     Owner:  NLM     Status:  MEDLINE    
Essential hypertension is a proinflammatory, proconstrictor disease coinciding with endothelial dysfunction and inward vessel remodeling. Using the skin circulation, our aim was to determine whether inducible NO synthase (iNOS) upregulation attenuates NO-dependent cutaneous vasodilation in hypertensive humans. We hypothesized that, with hypertension, localized iNOS inhibition would restore vasodilation in response to NO-dependent stimuli, and iNOS expression would be increased and phosphorylated vasodilator-stimulated phosphoprotein would be decreased. For, in vivo protocols, 4 intradermal microdialysis fibers were placed in 9 hypertensive and 10 normotensive men and women (systolic blood pressure: 146±4 versus 113±2 mm Hg; P<0.001). Microdialysis fibers served as control, iNOS inhibited (1400 W), neuronal NO synthase inhibited (N(ω)-propyl-l-arginine), and nonselective NOS inhibited (N(G)-nitro-l-arginine methyl ester). Cutaneous vascular conductance was calculated (percentage of sodium nitroprusside) during standardized local heating (42°C) and acetylcholine dose-response protocols (0.01, 0.10, 1.00, 5.00, 10.00, 50.00, 100.00 mmol/L). The NO-dependent local heating response was attenuated at control (95±2% versus 76±2% cutaneous vascular conductance; P<0.05) and neuronal NO synthase-inhibited sites (94±4% versus 77±3% cutaneous vascular conductance; P<0.01) in hypertensives. iNOS inhibition augmented the NO-dependent local heating response (93±2% versus 89±10% cutaneous vascular conductance). Acetylcholine-induced vasodilation was attenuated in control sites at doses ≥0.1 mmol/L of acetylcholine in hypertensives and was restored with iNOS inhibition (0.1 mmol/L, P<0.05; 1, 5, and 10 mmol/L, P<0.001; 50 and 100 mmol/L, P<0.01). In vitro iNOS expression was increased (P=0.006) and phosphorylated vasodilator-stimulated phosphoprotein was decreased in skin from hypertensive humans (P=0.04). These data suggest that iNOS is upregulated in essential hypertensive humans and contributes to reduced NO-dependent cutaneous vasodilation.
Caroline J Smith; Lakshmi Santhanam; Rebecca S Bruning; Anna Stanhewicz; Dan E Berkowitz; Lacy A Holowatz
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2011-09-19
Journal Detail:
Title:  Hypertension     Volume:  58     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-10-21     Completed Date:  2011-12-15     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  935-42     Citation Subset:  IM    
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MeSH Terms
Administration, Cutaneous
Analysis of Variance
Blotting, Western
Case-Control Studies
Dose-Response Relationship, Drug
Hypertension / enzymology*,  physiopathology
Laser-Doppler Flowmetry
Middle Aged
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide Synthase Type II / metabolism*
Nitroprusside / pharmacology
Reference Values
Regional Blood Flow / drug effects
Skin / blood supply*,  drug effects
Up-Regulation / drug effects*
Vasodilation / drug effects,  physiology*
Grant Support
R01 HL093238/HL/NHLBI NIH HHS; R01 HL093238-01/HL/NHLBI NIH HHS; R01 HL093238-02/HL/NHLBI NIH HHS; R01-HL093238-02/HL/NHLBI NIH HHS; UL1 TR000127/TR/NCATS NIH HHS
Reg. No./Substance:
169D1260KM/Nitroprusside; EC Oxide Synthase Type II; V55S2QJN2X/NG-Nitroarginine Methyl Ester

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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