title: Pharmacological curve fitting to analyze cutaneous adrenergic responses.
abstract: 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/m(2)) 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(-3) logM). 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, and 3) percent change from baseline without modeling. Not all data conformed to sigmoidal dose-response curves using analysis 1, whereas all subjects' curves were modeled using analysis 2. When analyzing only curves that fit the sigmoidal model, NE + KETO induced a leftward shift in ED(50) compared with NE alone with analyses 1 and 2 (F test, P < 0.05) but only tended to shift the response leftward with analysis 3 (repeated-measures ANOVA, P = 0.08). Neither maximal vasoconstrictor capacity (E(max)) in analysis 1 nor %change CVC change from baseline in analysis 3 were 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 2 produced more sigmoidal curves.
authors.affiliation: The John B. Pierce Laboratory, New Haven, CT, USA. mwenner@jbpierce.org
authors.forename: Megan M
authors.initials: MM
authors.lastname: Wenner
authors.forename: Thad E
authors.initials: TE
authors.lastname: Wilson
authors.forename: Scott L
authors.initials: SL
authors.lastname: Davis
authors.forename: Nina S
authors.initials: NS
authors.lastname: Stachenfeld
mesh_terms: D000322:Adrenergic Agonists / Q000008:administration & dosage*; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D020911:Ketorolac Tromethamine / Q000008:administration & dosage; D017551:Microdialysis; D017711:Nonlinear Dynamics; D009638:Norepinephrine / Q000008:administration & dosage; D012867:Skin / Q000098:blood supply* / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D055815:Young Adult; D019323:omega-N-Methylarginine / Q000008:administration & dosage
chemical_list: D000322:Adrenergic Agonists; D014662:Vasoconstrictor Agents; D019323:omega-N-Methylarginine; D020911:Ketorolac Tromethamine; D009638:Norepinephrine