Bradykinin is a potent vasodilator peptide that exerts the vasodilatory action through stimulation of specific endothelial B2 receptors, thereby causing the release of prostacyclin, NO, and Endothelium-derived hyperpolarization factor[1]. Bradykinin is associated with the pathological physiological processes accompanying tissue damage and inflammation, and has been used as a regulator in studies on pain and hyperalgesia[2].
In vitro, Bradykinin treatment at 1µM for 16 hours significantly enhanced cell invasion and migration of SW480 cells, and stimulated the activation of ERK1/2 and the production of IL-6 in SW480 cells[3]. Treatment with 1 µM Bradykinin for 24 hours significantly increased the expression of tissue factor and plasminogen activator inhibitor-1 (PAI-1) at both mRNA and protein levels in rat aortic endothelial cells (RAEC)[4]. The treatment with Bradykinin (0.001µM) for 24 hours significantly reduced the senescence of cultured bovine aortic endothelial cells induced by 25μM H2O2, which was manifested by the complete inhibition of the increase in the number of senescent cells and a remarkable decrease in the level of the senescence-associated cell cycle protein p21[5].
In vivo, Bradykinin treatment via intraperitoneal injection at dose of 10mg/kg/day for 5 days significantly reduced the expression of fibrin, inhibiting deep vein thrombosis in mice with inferior cava vein ligation[6]. Intravenous injection of Bradykinin (40µg/kg) in mice can inhibit bronchial contraction caused by acetylcholine (0.5mg/kg; intravenous injection) within 15min[7].
References:
[1] Hornig B, Kohler C, Drexler H. Role of bradykinin in mediating vascular effects of angiotensin-converting enzyme inhibitors in humans[J]. Circulation, 1997, 95(5): 1115-1118.
[2] Dray A, Perkins M. Bradykinin and inflammatory pain[J]. Trends in neurosciences, 1993, 16(3): 99-104.
[3] Wang G, Ye Y, Zhang X, et al. Bradykinin stimulates IL-6 production and cell invasion in colorectal cancer cells[J]. Oncology reports, 2014, 32(4): 1709-1714.
[4] Kimura S, Tsuji H, Nishimura H, et al. Bradykinin enhances in vitro procoagulant and antifibrinolytic properties of rat vascular endothelial cells[J]. Thrombosis research, 2002, 106(1): 41-50.
[5] Oeseburg H, Iusuf D, van der Harst P, et al. Bradykinin protects against oxidative stress–induced endothelial cell senescence[J]. Hypertension, 2009, 53(2): 417-422.
[6] Dong R, Chen W, Feng W, et al. Exogenous bradykinin inhibits tissue factor induction and deep vein thrombosis via activating the eNOS/phosphoinositide 3-kinase/Akt signaling pathway[J]. Cellular Physiology and Biochemistry, 2015, 37(4): 1592-1606.
[7] Folkerts G, van Heuven-Nolsen D, Nijkamp F P. Bradykinin causes inhibition of methacholine-induced bronchoconstriction in vivo in mice[J]. Naunyn-Schmiedeberg's Archives of Pharmacology, 2001, 364(1): 53-58.
Bradykinin是一种强效血管舒张肽，通过刺激特异性内皮B2受体发挥血管舒张作用，诱导前列环素、一氧化氮和内皮衍生超极化因子的释放[1]。Bradykinin参与组织损伤和炎症相关的病理生理过程，常作为疼痛和痛觉过敏研究的调节剂[2]。
在体外，1µM的Bradykinin处理16小时可显著增强SW480细胞的侵袭和迁移能力，并激活ERK1/2通路及促进IL-6生成[3]。1µM的Bradykinin处理24小时能显著提高大鼠主动脉内皮细胞（RAEC）组织因子和纤溶酶原激活物抑制因子-1（PAI-1）的mRNA及蛋白表达水平[4]。0.001µM的Bradykinin处理24小时可显著抑制25μM H2O2诱导的牛主动脉内皮细胞衰老，完全阻止衰老细胞数量增加并显著降低衰老相关细胞周期蛋白p21水平[5]。
在体内，腹腔注射Bradykinin（10mg/kg/day，持续5天）可显著抑制小鼠下腔静脉结扎模型中的纤维蛋白表达，减少深静脉血栓形成[6]。静脉注射Bradykinin（40µg/kg）能在15分钟内抑制乙酰胆碱（0.5mg/kg;静脉注射）引起的小鼠支气管收缩[7]。