New approach to measure cutaneous microvascular function: an improved test of NO-mediated vasodilation by thermal hyperemia

J Appl Physiol (1985). 2014 Aug 1;117(3):277-83. doi: 10.1152/japplphysiol.01397.2013. Epub 2014 Jun 5.


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.

Keywords: axon reflex; endothelial function; endothelial-derived hyperpolarizing factors; laser-doppler flowmetry; nitric oxide.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Female
  • Hot Temperature
  • Humans
  • Hyperemia / metabolism
  • Hyperemia / physiopathology*
  • Male
  • Microdialysis / methods
  • Microvessels / metabolism
  • Microvessels / physiology*
  • NG-Nitroarginine Methyl Ester / metabolism
  • Nitric Oxide / metabolism*
  • Regional Blood Flow / physiology
  • Skin / blood supply*
  • Skin / metabolism
  • Skin / physiopathology
  • Skin Physiological Phenomena
  • Vasodilation / physiology*
  • Young Adult


  • Nitric Oxide
  • NG-Nitroarginine Methyl Ester