Quantification and interpretation of nitric oxide-dependent cutaneous vasodilation during local heating.

Human cutaneous microdialysis approaches for assessing nitric oxide (NO)-dependent blood flow include local heating (LH) of the skin until a plateau is reached, followed by infusion of a NO synthase inhibitor such as -nitro-l-arginine methyl ester (l-NAME); however, varied methods of quantifying and expressing NO-dependent vasodilation can obfuscate data interpretation and reproducibility. We retrospectively assessed NO-dependent vasodilation during LH to 39°C or 42°C, calculated as the ) absolute contribution of the NO-dependent component (along with baseline and the non-NO-dependent component) to the total cutaneous vascular conductance (CVC) response to LH, normalized to maximal CVC (%CVC); ) difference in %CVC (Δ%CVC) between the LH plateau and post-NO synthase inhibition (l-NAME plateau; Δ%CVC = LH plateau - l-NAME plateau); ) percentage of the LH plateau attributable to Δ%CVC (%plateau = Δ%CVC/LH plateau × 100); and ) %plateau when correcting for baseline. The LH plateaus during 39°C and 42°C were 48 ± 17%CVC (9 ± 5% baseline; 2 ± 4% non-NO dependent; 36 ± 15% NO dependent) and 88 ± 10%CVC (15 ± 8% baseline; 9 ± 10% non-NO dependent; 64 ± 13% NO dependent), respectively. The absolute contributions of the non-NO-dependent and NO-dependent components of the response ( < 0.0001) and the Δ%CVC (66 ± 14 vs. 38 ± 15%) were greater during 42°C compared with 39°C (all ≤ 0.02); however, there were no differences between the two protocols in %plateau (75 ± 13 vs. 80 ± 10%; = 0.57) or %plateau (88 ± 14 vs. 95 ± 8%; = 0.31). For both protocols, the values were greater for %plateau versus Δ%CVC and %plateau ( ≤ 0.0001), and for %plateau versus Δ%CVC ( ≤ 0.05). Quantification of NO-dependent skin vasodilation responses to LH is dependent upon the mathematical approach and verbal description, which can meaningfully impact data interpretation and reproducibility. Local heating protocols are commonly used in conjunction with intradermal microdialysis for assessing nitric oxide (NO)-dependent microvascular function in humans, but various methods used to quantify and describe NO-dependent vasodilation may impact data interpretation. We compared four approaches for quantifying NO-dependent cutaneous vasodilation during local heating at 39°C and 42°C. We identify discrepancies in calculated NO-dependent dilation responses that are dependent upon the mathematical approach and meaningfully impact data interpretation and reproducibility.