A human vascular model based on microdialysis for the assessment of the vasoconstrictive dose-response effects of noradrenaline and vasopressin in skin : in JOURNAL OF VASCULAR RESEARCH, vol 48, pp 320-320

• Microdialysis is a well-established technique for continuous sampling of small, water-soluble molecules within the extracellular fluid space in vivo. It also allows the use of microdoses of drugs, and the simultaneous evaluation of their related effects at the site of action. The present study was an experimental, randomized microdose trial to develop a human vascular model of dose response. We aimed to evaluate a microdialysis dosing method using urea clearance as a marker of druginduced changes in dermal blood flow and metabolism (glucose and lactate) in 12 healthy volunteers. We found that asymptomatic vasoconstriction can be detected by continuous microdialysis measurements of urea clearance in dermal tissue. More importantly, dose-effect relations using the Emax model could be constructed using the corresponding data on drug doses and both the urea clearance-based flow estimates and the changes in concentrations of tissue metabolites. This in vivo human experimental skin model offers an interesting tool with which both the dose-response effects on blood flow and concentrations of tissue metabolites of potent vasoactive substances can be evaluated.

Nyckelord

Microdialysis; Urea; Skin; Noradrenalin; Vasopressin; micro dose; dose-response; pharmacodynamics; human; vasoconstriction

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