title: New approach to measure cutaneous microvascular function: an improved test of NO-mediated vasodilation by thermal hyperemia.
abstract: 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.
authors.affiliation: Department of Human Physiology, University of Oregon, Eugene, Oregon.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Choi
authors.affiliation: Department of Human Physiology, University of Oregon, Eugene, Oregon.
authors.forename: Vienna E
authors.initials: VE
authors.lastname: Brunt
authors.affiliation: Department of Human Physiology, University of Oregon, Eugene, Oregon.
authors.forename: Naoto
authors.initials: N
authors.lastname: Fujii
authors.affiliation: Department of Human Physiology, University of Oregon, Eugene, Oregon minson@uoregon.edu.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Minson
mesh_terms: D000328:Adult; D005260:Female; D006358:Hot Temperature; D006801:Humans; D006940:Hyperemia / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D017551:Microdialysis / Q000379:methods; D055806:Microvessels / Q000378:metabolism / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D012039:Regional Blood Flow / Q000502:physiology; D012867:Skin / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology; D012879:Skin Physiological Phenomena; D014664:Vasodilation / Q000502:physiology*; D055815:Young Adult
chemical_list: D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester
keywords: axon reflex; endothelial function; endothelial-derived hyperpolarizing factors; laser-doppler flowmetry; nitric oxide