Pharmacological curve fitting to analyze cutaneous adrenergic responses.
Pharmacological curve fitting to analyze cutaneous adrenergic responses.
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药理学曲线拟合分析皮肤肾上腺素能反应。
DOI：
10.1152/japplphysiol.00780.2011
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发表时间：
2011
期刊：
影响因子：
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通讯作者：
Stachenfeld,NinaS
中科院分区：
文献类型：
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作者：
Wenner,MeganM;Wilson,ThadE;Davis,ScottL;Stachenfeld,NinaS
尽管剂量-反应曲线通常用于描述体内皮肤α-肾上腺素能反应，但各研究的建模参数和分析方法并不一致。本研究的目的是使用一个参考数据集比较三种分析方法在体内皮肤血管收缩研究。8名女性（22 ± 1岁，24 ± 1 kg/m2）使用3个皮肤微透析探头进行去甲肾上腺素（NE）输注（1 × 10−8、1 × 10−6、1 × 10−5、1 × 10−4和1 × 10−3logM）。NE单独输注，与NG-单甲基-L-精氨酸（1-NMMA，10 mM）或酮咯酸氨丁三醇（KETO，10 mM）共同输注。对于每种探针，使用三种常用的分析方法生成剂量-反应曲线：1）无数据处理的非线性建模，2）数据归一化和约束的非线性建模，以及3）无建模的基线百分比变化。并非所有数据都符合分析1中的S形剂量-反应曲线，而所有受试者的曲线均采用分析2建模。当仅分析符合S形模型的曲线时，NE + Keto与NE单独给药相比，在分析1和分析2中诱导了ED 50的1/4偏移（F检验，P< 0.05），但在分析3中仅倾向于偏移响应1/4（重复测量ANOVA，P= 0.08）。阻断剂对分析1中的最大血管收缩能力（Emax）和分析3中的CVC相对于基线的变化百分比均无影响。总之，尽管两种曲线拟合建模方法的曲线偏移和解释的总体检测相似，但分析2产生了更多的S形曲线。
Although dose-response curves are commonly used to describe in vivo cutaneous α-adrenergic responses, modeling parameters and analyses methods are not consistent across studies. The goal of the present investigation was to compare three analysis methods for in vivo cutaneous vasoconstriction studies using one reference data set. Eight women (22 ± 1 yr, 24 ± 1 kg/m2) were instrumented with three cutaneous microdialysis probes for progressive norepinephrine (NE) infusions (1 × 10−8, 1 × 10−6, 1 × 10−5, 1 × 10−4, and 1 × 10−3logM). NE was infused alone, co-infused with NG-monomethyl-l-arginine (l-NMMA, 10 mM) or Ketorolac tromethamine (KETO, 10 mM). For each probe, dose-response curves were generated using three commonly reported analyses methods:1) nonlinear modeling without data manipulation,2) nonlinear modeling with data normalization and constraints, and3) percent change from baseline without modeling. Not all data conformed to sigmoidal dose-response curves usinganalysis 1, whereas all subjects' curves were modeled usinganalysis 2. When analyzing only curves that fit the sigmoidal model, NE + KETO induced a leftward shift in ED50compared with NE alone withanalyses 1and2(Ftest,P< 0.05) but only tended to shift the response leftward withanalysis 3(repeated-measures ANOVA,P= 0.08). Neither maximal vasoconstrictor capacity (Emax) inanalysis 1nor %change CVC change from baseline inanalysis 3were altered by blocking agents. In conclusion, although the overall detection of curve shifts and interpretation was similar between the two modeling methods of curve fitting,analysis 2produced more sigmoidal curves.