缓激肽引起的犬隐静脉收缩：由B2受体介导且类花生酸参与其中。

Bradykinin-induced contractions of canine saphenous veins: mediation by B2 receptors and involvement of eicosanoids.

作者信息

Marsault R, Illiano S, Vanhoutte P M

机构信息

Center for Experimental Therapeutics, Baylor College of Medicine, Houston, Texas, USA.

出版信息

Br J Pharmacol. 1997 Jan;120(2):215-20. doi: 10.1038/sj.bjp.0700898.

DOI:10.1038/sj.bjp.0700898

PMID:9117112

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1564372/

Abstract

Experiments were designed to determine the subtype of kinin-receptors mediating the contraction of venous smooth muscle to bradykinin and to investigate the involvement of metabolites of arachidonic acid in this response. 2. Bradykinin (10(-9) to 10(-6) M) caused concentration-dependent contractions of the canine isolated saphenous vein without endothelium, which were potentiated by indomethacin (10(-5) M, an inhibitor of cyclo-oxygenase). The concentration-response curve was biphasic, reaching an asymptote at 10(-8) M and a secondary maximal response at 10(-6) M. 3. Bradykinin (10(-8) M to 3 x 10(-6) M) caused a three fold stimulation in the release of the vasodilator prostaglandin E2 (PGE2) and a two fold stimulation of that of the vasodilator prostacyclin, measured by the production of 6-keto-PGF1 alpha (its stable breakdown product). 4. Under control conditions, nordihydroguaiaretic acid (NDGA, 10(-5) M), an inhibitor of lipoxygenase, did not affect the response to bradykinin. In the presence of indomethacin (10(-5) M), NDGA reduced contractions to bradykinin, suggesting the involvement of lipoxygenase metabolites in the potentiation evoked by the inhibitor of cyclo-oxygenase. 5. The selective B1 receptor agonist [des-Arg9]-bradykinin, in the concentration-range 10(-6) to 10(-5) M, induced contractions, which were abolished by the B2 receptor antagonist D-Arg-[Hyp3, Thi5, D-Tic7, Oic8]-bradykinin (Hoe 140; 10(-6) M). The selective B1 receptor antagonist [des-Arg9, Leu8]-bradykinin, (10(-7) to 10(-5) M) had no significant effect on bradykinin-induced contractions. 6. The B2 receptor antagonists Hoe 140 (10(-8) to 10(-6) M) and D-Arg [Hyp3, D-Phe7]-bradykinin (10(-7) to 10(-5) M) shifted the concentration-response curve to bradykinin to the right in a concentration-dependent manner. 7. These results indicate that, in the canine saphenous vein, bradykinin causes contraction by activating B2 receptors. This results in the production of metabolites of arachidonic acid, which play a key role in the contraction of canine saphenous venous smooth muscle.

摘要

设计实验以确定介导静脉平滑肌对缓激肽收缩反应的激肽受体亚型，并研究花生四烯酸代谢产物在此反应中的作用。2. 缓激肽（10⁻⁹至10⁻⁶M）可引起犬离体无内皮隐静脉浓度依赖性收缩，吲哚美辛（10⁻⁵M，一种环氧化酶抑制剂）可增强此收缩。浓度 - 反应曲线呈双相，在10⁻⁸M时达到渐近线，在10⁻⁶M时出现第二个最大反应。3. 缓激肽（10⁻⁸M至3×10⁻⁶M）可使血管舒张性前列腺素E2（PGE2）的释放增加三倍，并使血管舒张性前列环素的释放增加两倍，通过6 - 酮 - PGF1α（其稳定降解产物）的生成来测定。4. 在对照条件下，脂氧合酶抑制剂去甲二氢愈创木酸（NDGA，10⁻⁵M）不影响对缓激肽的反应。在吲哚美辛（10⁻⁵M）存在的情况下，NDGA可降低对缓激肽的收缩反应，提示脂氧合酶代谢产物参与环氧化酶抑制剂所引起的增强作用。5. 选择性B1受体激动剂[去 - Arg9] - 缓激肽，在10⁻⁶至10⁻⁵M浓度范围内可诱导收缩，该收缩可被B2受体拮抗剂D - Arg - [Hyp3, Thi5, D - Tic7, Oic8] - 缓激肽（Hoe 140；10⁻⁶M）消除。选择性B1受体拮抗剂[去 - Arg9, Leu8] - 缓激肽（10⁻⁷至10⁻⁵M）对缓激肽诱导的收缩无显著影响。6. B2受体拮抗剂Hoe 140（10⁻⁸至10⁻⁶M）和D - Arg [Hyp3, D - Phe7] - 缓激肽（10⁻⁷至10⁻⁵M）可使缓激肽的浓度 - 反应曲线以浓度依赖性方式右移。7. 这些结果表明，在犬隐静脉中，缓激肽通过激活B2受体引起收缩。这导致花生四烯酸代谢产物的产生，其在犬隐静脉平滑肌收缩中起关键作用。