Schumacher W A, Heran C L, Allen G T, Ogletree M L
Department of Pharmacology, Squibb Institute for Medical Research, Princeton, NJ 08543-4000.
Prostaglandins. 1989 Sep;38(3):335-44. doi: 10.1016/0090-6980(89)90137-8.
Thromboxane A2/prostaglandin H2 (TP)-receptor activation has been reported to participate in some of the responses to peptide leukotrienes (LT). We examined the effect of TP-receptor antagonism on LT-induced mesenteric vasoconstriction and hemoconcentration in anesthetized rats. The antagonist used in these studies, SQ 30,741, was shown to have high selectivity and potency for vascular TP-receptors in the rat. Arterial (i.a.) injection of LTC4 and D4 elicited dose-dependent and transient reductions in mesenteric blood flow without changes in arterial blood pressure. These responses were unaffected by a dose of SQ 30,741 which produced approximately 99% inhibition of similar responses to U-46,619. In contrast, LT-induced mesenteric vasoconstriction was inhibited approximately 90% by two LT antagonists, LY 171,883 and SKF 104,353. In other experiments i.v. infusion of LTD4 caused increases in hematocrit and reductions in arterial blood pressure that were not influenced by SQ 30,741. These data suggest that increases in mesenteric vascular resistance and hemoconcentration in response to LTs are not the result of TP-receptor activation.
据报道，血栓素A2/前列腺素H2（TP）受体激活参与了对肽白三烯（LT）的一些反应。我们研究了TP受体拮抗作用对麻醉大鼠LT诱导的肠系膜血管收缩和血液浓缩的影响。这些研究中使用的拮抗剂SQ 30,741对大鼠血管TP受体具有高选择性和效力。动脉内（i.a.）注射LTC4和D4引起肠系膜血流量剂量依赖性和短暂性降低，而动脉血压无变化。这些反应不受一定剂量的SQ 30,741的影响，该剂量对类似U-46,619的反应产生约99%的抑制。相比之下，两种LT拮抗剂LY 171,883和SKF 104,353对LT诱导的肠系膜血管收缩的抑制率约为90%。在其他实验中，静脉输注LTD4导致血细胞比容增加和动脉血压降低，这些均不受SQ 30,741的影响。这些数据表明，对LT反应的肠系膜血管阻力增加和血液浓缩不是TP受体激活的结果。
