Histamine response and local cooling in the human skin: involvement of H1- and H2-receptors.
OBJECTIVE
Histamine may contribute locally to cutaneous blood flow control under normal and pathologic conditions. The objective of this study was to observe the influence of skin temperature on histamine vasodilation, and the roles of H1-and H2-receptors using novel noninvasive methods.


METHODS
Eleven healthy subjects received, double-blind, single doses of the H1-receptor antagonist cetirizine (10 mg), cetirizine (10 mg) plus the H2-receptor antagonist cimetidine (400 mg), or placebo on separate occasions. Histamine was dosed cumulatively by iontophoresis to the forearm skin at 34 degrees C and 14 degrees C. Laser-Doppler flux (LDF) was measured at the same sites using customised probeholder/iontophoretic chambers with Peltier cooling elements. Finger mean arterial pressure (MAP) was measured and cutaneous vascular conductance calculated as LDF/MAP.


RESULTS
Histamine vasodilation was reduced in cold skin. Cetirizine shifted the histamine dose-response at both temperatures: statistically significantly at 14 degrees C only. Combined H1- and H2-receptor antagonism shifted the response significantly at both temperatures.


CONCLUSIONS
H1- and H2-receptors mediate histamine-induced skin vasodilation. The sensitivity of these receptors, particularly the H1- receptor, is attenuated at low skin temperature. Whether the reduced effect in cold skin represents specific receptor or postreceptor desensitization, or nonspecific attenuation of cutaneous vasodilation remains to be elucidated.
Institute of Clinical Pharmacology, Faculty of Medicine, University of Technology, Dresden, Germany.
M
M
Grossmann
M J
MJ
Jamieson
W
W
Kirch
D000328:Adult; D017332:Cetirizine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D003080:Cold Temperature; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007478:Iontophoresis; D017078:Laser-Doppler Flowmetry; D008297:Male; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000502:physiology*; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000098:blood supply / Q000187:drug effects; D012879:Skin Physiological Phenomena / Q000187:drug effects*
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D002927:Cimetidine; D017332:Cetirizine