VASCULAR EFFECTS OF LEUKOTRIENE-D4 IN HUMAN-SKIN
VASCULAR EFFECTS OF LEUKOTRIENE-D4 IN HUMAN-SKIN
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DOI：
10.1111/1523-1747.ep12525225
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发表时间：
1987-02-01
影响因子：
6.5
通讯作者：
BISGAARD, H
中科院分区：
文献类型：
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作者：
BISGAARD, H
白三烯D4（LTD 4）在3.1-200 pmol的剂量范围内增加人皮肤中的血流速率，与组胺等效。血管舒张持续长达60 min，无迟发反应发生。吲哚美辛不影响LTD 4诱导的血流速率。H1和H2拮抗剂降低了血液流速的增加，但没有消除对LTD 4的反应。局部神经阻滞抑制了LTD 4诱导的血流速度的轴突反射介导的闪光成分，留下局部红色反应。这种局部红色反应不受H1和H2拮抗剂的影响。这些结果表明组胺作为轴突反射的介质，并表明LTD 4引起不通过组胺或环氧合酶产物介导的直接血管舒张作用。应用激光多普勒血流计对Valsalva动作时皮肤的血管加压反应进行动态研究，并通过133氙冲洗法对血流速率进行控制估计来证实血流的相对变化。局部神经阻滞可逆转Valsalva动作的升压反应，但不受LTD 4的影响。因此，LTD 4不干扰皮肤血管上的交感神经活动。白三烯D4引起剂量依赖性风团反应，在0.2-200 pmol剂量范围内与组胺等效。当注射LTD 4之前试验臂的血管系统被阻塞时，仅发生轻微的风团，30分钟后循环恢复。大部分LTD 4显然在此期间代谢。随后向相同部位注射LTD 4证明了风团形成的快速耐受性。这一证据表明LTD 4不能介导持续的炎症。LTD 4的注射既不引起疼痛也不引起瘙痒。总之，阐明的属性指向LTD 4作为急性炎症期间微血管变化的可能介质。
Leukotriene D4 (LTD4) increased the blood flow rate in human skin, equipotent to histamine in the dose range of 3.1-200 pmol. The vasodilatation lasted for up to 60 min, and no late reactions occurred. Indomethacin did not affect the LTD4-induced blood flow rate. H1 and H2 antagonists reduced the increase in blodo flow rate, but did not abolish the response to LTD4. Local nerve block inhibited the axon reflex-mediated flare component of the LTD4-induced blood flow rate, leaving a local red reaction. This local red reaction was not affected by H1 and H2 antagonists. These results indicate histamine as a mediator of the axon reflex, and show that LTD4 causes a direct vasodilatory effect that is not mediated via histamine or cyclooxygenase products. The laser-Doppler flowmeter was applied for dynamic studies of the vasopressor response in the skin during a Valsalva maneuver, and the relative changes in blood flow were confirmed by control estimates of the blood flow rate by a 133xenon washout method. The pressor response to a Valsalva maneuver was reversed by local nerve block, but not affected by LTD4. Therefore LTD4 did not interfere with the sympathetic activity on the cutaneous vessels. Leukotriene D4 caused a dose-dependent wheal reaction, equipotent to histamine in the dose range of 0.2-200 pmol. Only minor whealing occurred when the vasculature to the test arm was occluded before injection of LTD4 and the circulation restored 30 min later. Most of the LTD4 was apparently metabolized within this period. Subsequent injections of LTD4 into the same sites demonstrated the development of tachyphylaxis with respect to whealing. This evidence suggests that LTD4 cannot mediate sustained inflammation. The injections of LTD4 caused neither pain nor itching. In conclusion, the elucidated properties point to LTD4 as possible mediator of microvascular changes during acute inflammation.