More Amar S, Kim Hye Min, Zhao Ru, Khang Gilson, Hildebrandt Tobias, Bernlöhr Christian, Doods Henri, Lee Dongwon, Lee Seung Hee, Vanhoutte Paul M, Wu Dongmei
*WCU program, Department of BIN Fusion Technology, Chonbuk National University, Chonju, Korea; †CNS Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany; and ‡Department of Pharmacology, University of Hong Kong, Hong Kong, China.
J Cardiovasc Pharmacol. 2014 Sep;64(3):209-17. doi: 10.1097/FJC.0000000000000105.
This study examined the vascular effects of bradykinin in health and vascular inflammation comparing responses of isolated pig coronary arteries in the absence and presence of endotoxins. Bradykinin induced contractions in lipopolysaccharide-treated, but not untreated, arterial rings without endothelium. The B2-receptor antagonist HOE140, but not the B1-receptor inhibitor SSR240612, blocked these endothelium-independent contractions in response to bradykinin. The bradykinin-induced contractions were blocked by indomethacin, celecoxib, and terbogrel but not valeryl salicylate, AH6809, AL 8810, or RO1138452. They were attenuated by N-(p-amylcinnamoyl) anthranilic acid, and by diethyldithiocarbamate plus tiron but not by L-NAME. Quantitative reverse-transcription polymerase chain reaction revealed significant upregulations of messenger RNA expressions of B1 receptors, COX-2, and thromboxane A synthase 1 (TBXAS1) following lipopolysaccharide incubation but not of B2 receptors or COX-1. The present data demonstrate that bradykinin induces contractions mediated by the COX-2 pathway in endotoxin-treated pig coronary arteries. These results support differential roles of bradykinin in health and disease.
本研究通过比较内毒素存在和不存在时分离的猪冠状动脉的反应，研究了缓激肽在健康和血管炎症中的血管效应。缓激肽在脂多糖处理而非未处理的无内皮动脉环中诱导收缩。B2受体拮抗剂HOE140而非B1受体抑制剂SSR240612可阻断缓激肽引起的这些非内皮依赖性收缩。缓激肽诱导的收缩可被吲哚美辛、塞来昔布和特波格雷尔阻断，但不能被戊酰水杨酸、AH6809、AL 8810或RO1138452阻断。它们被N-（对戊基肉桂酰基）邻氨基苯甲酸以及二乙基二硫代氨基甲酸盐加替诺尔减弱，但不被L-NAME减弱。定量逆转录聚合酶链反应显示，脂多糖孵育后，B1受体、COX-2和血栓素A合酶1（TBXAS1）的信使核糖核酸表达显著上调，但B2受体或COX-1的表达未上调。目前的数据表明，缓激肽在内毒素处理的猪冠状动脉中诱导由COX-2途径介导的收缩。这些结果支持缓激肽在健康和疾病中的不同作用。
