Skin microcirculatory effect of exogenous calcitonin gene-related peptide (CGRP) evaluated by laser Doppler flowmetry coupled with iontophoresis in healthy subjects.
The aim of our study was to evaluate the feasibility of laser Doppler flowmetry (LDF) coupled with iontophoresis in exploring the skin vasodilator activity of exogenous calcitonin gene-related peptide (CGRP) in healthy subjects and to investigate the mechanisms involved in the skin vasodilator activity of this peptide. Forearm skin blood perfusion was measured in conventional perfusion unit (PU; 1 PU=10 mV), using a LDF apparatus (Periflux PF4001, Perimed, Sweden), before and following exogenous CGRP dissolved in distilled water (0.02%) or pure saline iontophoresis. Different iontophoresis protocols were used in a preliminary dose finding study in six subjects. Two pulses (0.1 mA for 30 s each) of anodal CGRP or saline iontophoresis were used in the definitive study in 20 subjects. Power spectral density (PSD) of skin blood flowmotion frequency intervals (FI), related to endothelial (0.009-0.02 Hz), sympathetic (0.02-0.06 Hz), myogenic (0.06-0.2 Hz), respiratory (0.2-0.6 Hz) and heart (0.6-1.6 Hz) activities, was also measured in PU(2)/Hz, by means of spectral analysis of the skin LDF signal registered before and following iontophoresis of CGRP or saline in the definitive study. A significantly higher per cent increase in skin perfusion compared to baseline was observed following CGRP than saline iontophoresis (548+/-369% vs. 326+/-192%, p<0.05), with higher hyperaemic response to pure saline than CGRP iontophoresis in only five subjects. A significant increase (p<0.05) in PSD mean value of the five FI considered, was also observed following CGRP iontophoresis, while saline iontophoresis elicited a significant increase (p<0.05) only in PSD of the FI related to endothelial, respiratory and heart activity. These findings demonstrated that LDF coupled with iontophoresis is a feasible method in evaluating the vasodilator effect of exogenous CGRP in human skin and suggest that this peptide directly or indirectly induces a smooth muscle vascular cells and sympathetic fibres stimulation.
Rossi
M
M
Department of Internal Medicine, University of Pisa, Italy. mrossi@int.med.unipi.it
Carpi
A
A
Di Maria
C
C
Galetta
F
F
Santoro
G
G
D000328:Adult; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007478:Iontophoresis; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000098:blood supply* / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D011994:Recombinant Proteins; D015740:Calcitonin Gene-Related Peptide