title: Dose-dependent vasodilatory effects of acetylcholine and local warming on skin microcirculation.
abstract: The assessment of the skin microvasculature response to iontophoretically applied acetylcholine (ACh) and local warming makes it possible to explore noninvasively in humans the functional integrity of endothelium. The present study aimed to examine whether these two stimuli of nitric oxide (NO) release have a dose-dependent vasorelaxant activity. For this purpose we assessed in healthy subjects using a laser-Doppler imaging system the increase in forearm blood flow following transdermal application of increasing amounts of ACh [with an iontophoretic current of either 0.28 mC/cm2 (n = 18), 0.56 mC/cm2 (n = 14), 1.4 mC/cm2 (n = 26), 7 mC/cm2 (n = 14), 28 mC/cm2 (n = 14), or 48 mC/cm2 (n = 6)] or graded warming of the skin [to either 37 degrees C (n = 8), 39 degrees C (n = 4) or 41 degrees C (n = 12)]. The maximal vasodilation was significantly smaller with the lowest dose than with the higher doses of ACh, and a plateau was reached with the 1.4 mC/cm2 dose. The skin blood flow responses to ACh were not dependent on the pulsed or continuous pattern of iontophoretic administration. The hyperemia induced by the local heating to 41 degrees C was significantly greater than that observed with the other temperatures. When measured in the same subjects, the magnitude of the maximal ACh-mediated skin blood flow increase was significantly smaller than the vasodilation associated with the warming to 41 degrees C. In summary, transdermally applied ACh and local heating of the skin induce a dose-dependent vasorelaxation. These techniques represent a unique means to investigate noninvasively the functional vasodilatory capacity of the skin microvasculature.
authors.affiliation: Division of Clinical Pathophysiology, University Hospital, Lausanne, Switzerland.
authors.forename: Samuel
authors.initials: S
authors.lastname: Christen
authors.forename: Anne
authors.initials: A
authors.lastname: Delachaux
authors.forename: Benoît
authors.initials: B
authors.lastname: Dischl
authors.forename: Sandrine
authors.initials: S
authors.lastname: Golay
authors.forename: Lucas
authors.initials: L
authors.lastname: Liaudet
authors.forename: François
authors.initials: F
authors.lastname: Feihl
authors.forename: Bernard
authors.initials: B
authors.lastname: Waeber
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000328:Adult; D000779:Anesthetics, Local / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D006801:Humans; D007478:Iontophoresis; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D012867:Skin / Q000098:blood supply* / Q000187:drug effects; D012881:Skin Temperature / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000779:Anesthetics, Local; D014665:Vasodilator Agents; D000109:Acetylcholine