Department of Kinesiology, University of Georgia, Athens, Georgia, United States.
Department of Kinesiology, The Pennsylvania State University, University Park, Pennsylvania, United States.
J Appl Physiol (1985). 2024 Nov 1;137(5):1418-1424. doi: 10.1152/japplphysiol.00558.2024. Epub 2024 Oct 17.
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.
人体皮肤微透析方法评估一氧化氮（NO）依赖性血流包括局部加热（LH）皮肤，直到达到平台，然后输注一氧化氮合酶抑制剂，如 -硝基-L-精氨酸甲酯（L-NAME）; 然而，量化和表达 NO 依赖性血管舒张的方法各不相同可能会混淆数据解释和可重复性。我们回顾性评估了 LH 至 39°C 或 42°C 时的 NO 依赖性血管舒张，计算为绝对贡献的 NO 依赖性成分（与基线和非 NO 依赖性成分）对 LH 反应的皮肤血管传导率（CVC），归一化为最大 CVC（%CVC）; ）LH 平台和 NO 合酶抑制后（L-NAME 平台）之间的 %CVC 差异（Δ%CVC）; ）LH 平台归因于 Δ%CVC 的百分比（%plateau = Δ%CVC/LH 平台×100）; 和）基线校正后的 %plateau。39°C 和 42°C 时的 LH 平台分别为 48 ± 17% CVC（9 ± 5% 基线; 2 ± 4% 非 NO 依赖性; 36 ± 15% NO 依赖性）和 88 ± 10% CVC（15 ± 8% 基线; 9 ± 10% 非 NO 依赖性; 64 ± 13% NO 依赖性）。响应的非 NO 依赖性和 NO 依赖性成分的绝对贡献（<0.0001）和 Δ%CVC（66 ± 14 对 38 ± 15%）在 42°C 时大于 39°C（均 <0.02）; 然而，两种方案之间的 %plateau 没有差异（75 ± 13 对 80 ± 10%; = 0.57）或 %plateau（88 ± 14 对 95 ± 8%; = 0.31）。对于两种方案，%plateau 与 Δ%CVC 和 %plateau 的值均大于（<0.0001），而 %plateau 与 Δ%CVC 的值均大于（<0.05）。NO 依赖性皮肤血管舒张反应的量化取决于数学方法和描述，这可能会对数据解释和可重复性产生重大影响。局部加热方案常用于结合皮内微透析评估人类一氧化氮（NO）依赖性微血管功能，但用于量化和描述 NO 依赖性血管舒张的各种方法可能会影响数据解释。我们比较了在 39°C 和 42°C 时局部加热期间量化 NO 依赖性皮肤血管舒张的四种方法。我们发现计算出的 NO 依赖性扩张反应存在差异，这取决于数学方法，并对数据解释和可重复性产生重大影响。
