New approach to measure cutaneous microvascular function: an improved test of NO-mediated vasodilation by thermal hyperemia
Open accessAbstract
Cutaneous hyperemia in response to rapid skin local heating to 42°C has been used extensively to assess microvascular function. However, the response is dependent on both nitric oxide (NO) and endothelial-derived hyperpolarizing factors (EDHFs), and increases cutaneous vascular conductance (CVC) to ∼90–95% maximum in healthy subjects, preventing the study of potential means to improve cutaneous function. We sought to identify an improved protocol for isolating NO-dependent dilation. We compared nine heating protocols (combinations of three target temperatures: 36°C, 39°C, and 42°C, and three rates of heating: 0.1°C/s, 0.1°C/10 s, 0.1°C/min) in order to select two protocols to study in more depth ( protocol 1; N = 6). Then, CVC was measured at four microdialysis sites receiving: 1) lactated Ringer solution (Control), 2) 50-mM tetraethylammonium (TEA) to inhibit EDHFs, 3) 20-mM nitro-L-arginine methyl ester (L-NAME) to inhibit NO synthase, and 4) TEA+L-NAME, in response to local heating either to 39°C at 0.1°C/s ( protocol 2; N = 10) or 42°C at 0.1°C/min ( protocol 3; N = 8). Rapid heating to 39°C increased CVC to 43.1 ± 5.2%CVCmax (Control), which was attenuated by L-NAME (11.4 ± 2.8%CVCmax; P < 0.001) such that 82.8 ± 4.2% of the plateau was attributable to NO. During gradual heating, 81.5 ± 3.3% of vasodilation was attributable to NO at 40°C, but at 42°C only 32.7 ± 7.8% of vasodilation was attributable to NO. TEA+L-NAME attenuated CVC beyond L-NAME at temperatures >40°C (43.4 ± 4.5%CVCmax at 42°C, P < 0.001 vs. L-NAME), suggesting a role of EDHFs at higher temperatures. Our findings suggest local heating to 39°C offers an improved approach for isolating NO-dependent dilation and/or assessing perturbations that may improve microvascular function.
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Impaired endothelium-dependent vasodilation results not only in impaired macrovascular function, but also in microvascular dysfunction, as measured by retinal artery vasodilation and heat-induced skin hyperemia.
“Impaired endothelium-dependent vasodilation results not only in impaired macrovascular function, but also in microvascular dysfunction, as measured by retinal artery vasodilation and heat-induced skin hyperemia.”
From The Vasculature in Prediabetes (2018) · cites this paper as [106]
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The Vasculature in Prediabetes
Wasserman, D. H., Wang, T. J., & Brown, N. J. (2018) · Circulation Research · doi:10.1161/circresaha.118.311912 · Cited by 137 · see citing works
- Authors
- Choi, P. J., Brunt, V. E., Fujii, N., & Minson, C. T.
- Affiliations
- University of Oregon (US)
- Corresponding author
- Minson, Christopher T.
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 2014-08-01
- Volume
- 117
- Issue
- 3
- Pages
- 277-283
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- PMC
- PMC4122693
- OpenAlex
- W2128986918
- Cited by
- 123
- References
- 46
- Citations by year
- 2026: 12 · 2025: 8 · 2024: 9 · 2023: 12 · 2022: 12 · 2021: 13 · 2020: 17 · 2019: 9 · 2018: 8 · 2017: 6 · 2016: 8 · 2015: 6 · 2014: 3
- FWCI
- 5.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Applied Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL081671, R01HL081671)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Physiology › Thermoregulation and physiological responses
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- cutaneous microvascular function, nitric oxide, cutaneous vascular conductance, tetraethylammonium, L-NAME, NO synthase inhibition, microdialysis, vasodilation, heating rate, endothelium-dependent vasodilation
- MeSH terms
- Adult, Female, Hot Temperature, Humans, Hyperemia, Male, Nitric Oxide, Regional Blood Flow, Skin, Skin Physiological Phenomena, Vasodilation, Microdialysis, NG-Nitroarginine Methyl Ester, Microvessels, Young Adult
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