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

• Published in: Journal of applied physiology (1985) Vol. 117; no. 3; pp. 277 - 283
• Main Authors: Choi, Patricia J., Brunt, Vienna E., Fujii, Naoto, Minson, Christopher T.
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.08.2014
• Subjects: Adult; Comparative analysis; Female; Heating; High temperature; Hot Temperature; Humans; Hyperemia - metabolism; Hyperemia - physiopathology; Male; Microdialysis - methods; Microvessels - metabolism; Microvessels - physiology; NG-Nitroarginine Methyl Ester - metabolism; Nitric oxide; Nitric Oxide - metabolism; Regional Blood Flow - physiology; Skin - blood supply; Skin - metabolism; Skin - physiopathology; Skin Physiological Phenomena; Temperature; Vasodilation - physiology; Young Adult; endothelial function; endothelial-derived hyperpolarizing factors; nitric oxide; laser-doppler flowmetry; axon reflex
• ISSN: 8750-7587; 1522-1601; 1522-1601
• DOI: 10.1152/japplphysiol.01397.2013

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.