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Endothelial nitric oxide synthase mediates cutaneous vasodilation during local heating and is attenuated in middle-aged human skin
Journal article   Open access   Peer reviewed

Endothelial nitric oxide synthase mediates cutaneous vasodilation during local heating and is attenuated in middle-aged human skin

Rebecca S Bruning, Lakshmi Santhanam, Anna E Stanhewicz, Caroline J Smith, Dan E Berkowitz, W. Larry Kenney and Lacy A Holowatz
Journal of applied physiology (1985), Vol.112(12), pp.2019-2026
04/12/2012
DOI: 10.1152/japplphysiol.01354.2011
PMCID: PMC3378394
PMID: 22500004
url
https://doi.org/10.1152/japplphysiol.01354.2011View
Published (Version of record) Open Access

Abstract

Local skin heating is used to assess microvascular function in clinical populations because NO is required for full expression of the response; however, controversy exists as to the precise NO synthase (NOS) isoform producing NO. Human aging is associated with attenuated cutaneous vasodilation but little is known about the middle aged, an age cohort used for comparison with clinical populations. We hypothesized that endothelial NOS (eNOS) is the primary isoform mediating NO production during local heating, and eNOS-dependent vasodilation would be reduced in middle-aged skin. Vasodilation was induced by local heating (42°C) and during acetylcholine dose-response (ACh-DR: 0.01, 0.1, 1.0, 5.0, 10.0, 50.0, 100.0 mmol/l) protocols. Four microdialysis fibers were placed in the skin of 24 men and women; age cohorts were 12 middle-aged (53 ± 1 yr) and 12 young (23 ± 1 yr). Sites served as control, nonselective NOS inhibited [ N G -nitro- l -arginine methyl ester ( l -NAME)], inducible NOS (iNOS) inhibited (1400W), and neuronal NOS (nNOS) inhibited ( N ω -propyl- l -arginine). After full expression of the local heating response, l -NAME was perfused at all sites. Cutaneous vascular conductance was measured and normalized to maximum (%CVC max : Nitropress). l -NAME reduced %CVCmax at baseline, all phases of the local heating response, and at all ACh concentrations compared with all other sites. iNOS inhibition reduced the initial peak (53 ± 2 vs. 60 ± 2%CVC max ; P < 0.001); however, there were no other differences between control, nNOS-, and iNOS-inhibited sites during the phases of local heating or ACh-DR. When age cohorts were compared, NO-dependent vasodilation during local heating (52 ± 6 vs. 68 ± 4%CVC max ; P = 0.013) and ACh perfusion (50 mmol/l: 83 ± 3 vs. 93 ± 2%CVC max ; 100 mmol/l: 83 ± 4 vs. 92 ± 3%CVC max ; both P = 0.03) were reduced in middle-aged skin. There were no differences in NOS isoform expression obtained from skin biopsy samples between groups (all P > 0.05). These data suggest that eNOS mediates the production of NO during local heating and that cutaneous vasodilation is attenuated in middle-aged skin.
 inducible nitric oxide synthase neuronal nitric oxide synthase skin blood flow vascular aging

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