WCU program, Department of BIN Fusion Technology, Chonbuk National University, Chonju, Republic of Korea.
CNS Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
Pharmacol Res. 2014 Dec;90:18-24. doi: 10.1016/j.phrs.2014.09.001. Epub 2014 Sep 22.
This study examined responses of isolated pig coronary arteries after kinin B1 receptor induction by endotoxin. Des-Arg9-bradykinin (DBK) induced concentration-dependent, endothelium-independent contractions in lipopolysaccharide (LPS)-treated but not untreated arterial rings. The B1-receptor antagonist SSR240612, but not the B2-receptor antagonist HOE140, prevented the endothelium-independent contractions to DBK. The DBK-induced contractions were blocked by indomethacin (nonselective cyclooxygenase [COX] inhibitor), celecoxib (selective COX-2 inhibitor), and terbogrel (thromboxane-prostanoid [TP] receptor antagonist) but not valeryl salicylate (selective COX-1 inhibitor), AH6809 (an E prostanoid [EP] and PGD2 receptor [DP1] receptor antagonist), AL 8810 (a selective PGF2α [FP] receptor antagonist), or RO1138452 (a selective I prostanoid [IP] receptor antagonist). They were attenuated by N-(p-amylcinnamoyl) anthranilic acid (ACA), and by DETCA plus tiron but not by l-NAME. Quantitative RT-PCR revealed excessive up-regulations of mRNA expressions of B1 receptors, COX-2, and thromboxane A synthase 1 (TBXAS1) following LPS incubation, but not of B2 receptors or COX-1. The present data demonstrate that B1 receptors are coupled to COX-2 in causing endothelium-independent contractions in endotoxin-treated pig coronary arteries. Accordingly, kinin B1 receptor induction during inflammation may have a pathological significance in the vasculature, particular in coronary arteries with dysfunctional endothelial cells.
本研究探讨了内毒素诱导激肽 B1 受体后分离猪冠状动脉的反应。去精氨酸 9-缓激肽（DBK）在脂多糖（LPS）处理但未处理的动脉环中诱导浓度依赖性、内皮非依赖性收缩。B1 受体拮抗剂 SSR240612，但不是 B2 受体拮抗剂 HOE140，可防止 DBK 引起的内皮非依赖性收缩。DBK 诱导的收缩被吲哚美辛（非选择性环氧化酶 [COX]抑制剂）、塞来昔布（选择性 COX-2 抑制剂）和替罗格雷（血栓烷-前列腺素 [TP]受体拮抗剂）阻断，但 Valeryl 水杨酸盐（选择性 COX-1 抑制剂）、AH6809（E 前列腺素 [EP]和 PGD2 受体 [DP1]受体拮抗剂）、AL 8810（选择性 PGF2α [FP]受体拮抗剂）或 RO1138452（选择性 I 前列腺素 [IP]受体拮抗剂）不阻断。它们被 N-（对氨基肉桂酰）邻氨基苯甲酸（ACA）和 DETCA 加 tiron 减弱，但不受 l-NAME 影响。定量 RT-PCR 显示 LPS 孵育后 B1 受体、COX-2 和血栓烷 A 合酶 1（TBXAS1）的 mRNA 表达过度上调，但 B2 受体和 COX-1 没有上调。本研究数据表明，B1 受体与 COX-2 耦联，导致内毒素处理的猪冠状动脉内皮非依赖性收缩。因此，炎症期间激肽 B1 受体的诱导可能在血管系统中具有病理意义，特别是在功能失调的内皮细胞的冠状动脉中。
