Journal article
Upregulation of Inducible Nitric Oxide Synthase Contributes to Attenuated Cutaneous Vasodilation in Essential Hypertensive Humans
Hypertension (Dallas, Tex. 1979), Vol.58(5), pp.935-942
11/2011
DOI: 10.1161/HYPERTENSIONAHA.111.178129
PMCID: PMC3209704
PMID: 21931069
Abstract
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.
Details
- Title: Subtitle
- Upregulation of Inducible Nitric Oxide Synthase Contributes to Attenuated Cutaneous Vasodilation in Essential Hypertensive Humans
- Creators
- Caroline J. Smith - Pennsylvania State UniversityLakshmi Santhanam - Johns Hopkins University School of MedicineRebecca S. Bruning - Johns Hopkins University School of MedicineAnna Stanhewicz - Johns Hopkins University School of MedicineDan E. Berkowitz - Johns Hopkins University School of MedicineLacy A. Holowatz - Johns Hopkins University School of Medicine
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.58(5), pp.935-942
- DOI
- 10.1161/HYPERTENSIONAHA.111.178129
- PMID
- 21931069
- PMCID
- PMC3209704
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 11/2011
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Health and Human Physiology; Internal Medicine
- Record Identifier
- 9984259392202771
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