Grossmann M, Jamieson M J, Kirch W
Institute of Clinical Pharmacology, Faculty of Medicine, University of Technology, Dresden, Germany.
Br J Clin Pharmacol. 1999 Aug;48(2):216-22. doi: 10.1046/j.1365-2125.1999.00994.x.
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.
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.
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.
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.
在正常和病理条件下，组胺可能在局部对皮肤血流控制起作用。本研究的目的是使用新型非侵入性方法观察皮肤温度对组胺血管舒张的影响以及H1和H2受体的作用。
11名健康受试者在不同时间接受双盲单剂量的H1受体拮抗剂西替利嗪（10毫克）、西替利嗪（10毫克）加H2受体拮抗剂西咪替丁（400毫克）或安慰剂。通过离子电渗疗法在34℃和14℃下将组胺累积给药至前臂皮肤。使用带有珀尔帖冷却元件的定制探头支架/离子电渗腔室在相同部位测量激光多普勒血流（LDF）。测量手指平均动脉压（MAP），并将皮肤血管传导率计算为LDF/MAP。
在寒冷皮肤中组胺血管舒张作用减弱。西替利嗪在两个温度下均使组胺剂量反应发生偏移：仅在14℃时具有统计学显著性。H1和H2受体联合拮抗在两个温度下均使反应显著偏移。
H1和H2受体介导组胺诱导的皮肤血管舒张。这些受体，尤其是H1受体，在低皮肤温度下敏感性降低。寒冷皮肤中效应降低是代表特异性受体或受体后脱敏，还是皮肤血管舒张的非特异性减弱，仍有待阐明。
