POTENT VASOACTIVE PROPERTIES OF ENDOTHELIN-1 IN HUMAN SKIN

被引:31
作者
CROSSMAN, DC
BRAIN, SD
FULLER, RW
机构
[1] KINGS COLL,DIV BIOSCI,PHARMACOL GRP,CHELSEA CAMPUS,MANRESA RD,LONDON SW3 6LX,ENGLAND
[2] CLIN RES CTR,MRC,VASC BIOL SECT,HARROW HA1 3UJ,MIDDX,ENGLAND
[3] ROYAL POSTGRAD MED SCH,DEPT CLIN PHARMACOL,LONDON W12 0HS,ENGLAND
基金
英国惠康基金;
关键词
VASOCONSTRICTORS; BLOOD FLOW; AXON REFLEX FLARE;
D O I
10.1152/jappl.1991.70.1.260
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The effect of the endothelial cell-derived peptide endothelin 1 was investigated in human skin. Intradermal injection of endothelin 1 (1-100 pmol) caused a dose-dependent area of pallor that was associated with a significant reduction in basal skin blood flow, measured by laser-Doppler blood flowmeter (with 1 pmol endothelin, P = 0.012, analysis of variance). The coadministration of endothelin 1 (1-100 pmol) with the neuropeptide vasodilator calcitonin gene-related peptide (CGRP) inhibited the vasodilator response to CGRP (10 pmol) by up to 82.7 +/- 9.2% (with 100 pmol endothelin, P < 0.001). The response of the prostanoid vasodilator prostaglandin E2 (10 pmol) was inhibited by endothelin in a similar manner. In addition to the vasoconstrictor effects, endothelin 1 produced a dose-dependent flare that surrounded the area of pallor, and this was associated with a significant increase in blood flow (P < 0.05) within the flare area. The H1 antagonist terfenadine (120 mg po) significantly reduced the flare area associated with endothelin 1: flare 5 min after intradermal endothelin (10 pmol, placebo treated), 668 +/- 405 mm2; terfenadine treated, 201 +/- 257 mm2 (P < 0.05). The flare was also significantly attenuated when endothelin (10 pmol) was injected into local anesthetic-treated skin. Thus intradermal injection of endothelin in humans causes long-lasting vasoconstriction at the site of injection and a surrounding flare. Results suggest that the flare component is partially histamine dependent and the results of an axon reflex. This study demonstrates the potent activity of endothelin in human skin. It is possible that endothelin could be relevant to the local response of skin to injury.
引用
收藏
页码:260 / 266
页数:7
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