BW 755C和去甲二氢愈创木酸对大鼠离体灌注肠系膜血管系统的作用。

The effect of BW 755C and nordihydroguaiaretic acid in the rat isolated perfused mesenteric vasculature.

作者信息

Stanton B J, Coupar I M

出版信息

Prostaglandins Leukot Med. 1986 Dec;25(2-3):199-207. doi: 10.1016/0262-1746(86)90066-1.

Abstract

The suitability of two lipoxygenase inhibitors to study the putative effects of leukotrienes (LTs) in rat isolated perfused mesentery has been assessed. Both the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) and the dual lipoxygenase and cyclo-oxygenase inhibitor BW 755C depressed vasoconstrictor responses to NA, an effect characteristic of cyclo-oxygenase inhibitors on this tissue. However, depression of responses to NA by NDGA was non-selective since it depressed responses to calcium over the same concentration range. BW 755C possessed some selectivity for inhibition of responses to NA compared to calcium. The difference in relative selectivities between the two inhibitors was confirmed using prostaglandin E2 (PGE2), which reversed responses to NA depressed by BW 755C to a greater extent than those depressed by NDGA. LTC4 and LTD4 neither caused vasoconstriction nor reversed responses to NA depressed by BW 755C. Since NDGA in particular caused depression in this tissue, results using this drug to investigate the possible role of LTs in other blood vessels should be treated with caution.

摘要

评估了两种脂氧合酶抑制剂在大鼠离体灌注肠系膜中研究白三烯（LTs）假定作用的适用性。脂氧合酶抑制剂去甲二氢愈创木酸（NDGA）和脂氧合酶与环氧化酶双重抑制剂BW 755C均能抑制对去甲肾上腺素（NA）的血管收缩反应，这是环氧化酶抑制剂对该组织的典型作用。然而，NDGA对NA反应的抑制是非选择性的，因为它在相同浓度范围内也抑制对钙的反应。与钙相比，BW 755C对NA反应的抑制具有一定的选择性。使用前列腺素E2（PGE2）证实了两种抑制剂相对选择性的差异，PGE2使BW 755C抑制的NA反应恢复的程度大于NDGA抑制的反应。LTC4和LTD4既不引起血管收缩，也不能逆转BW 755C抑制的NA反应。由于NDGA尤其会导致该组织的抑制作用，因此使用该药物研究LTs在其他血管中可能作用的结果应谨慎对待。