Histamine response and local cooling in the human skin: involvement of H1‐ and H2‐receptors

Abstract

Aims 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° C and 14° 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° 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.