Bradykinin B-2 receptor involvement in rabbit and murine models of septic shock
Bradykinin B-2 receptor involvement in rabbit and murine models of septic shock
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DOI：
10.1097/00005344-199604000-00008
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发表时间：
1996-04-01
影响因子：
3
通讯作者：
Canet, E
中科院分区：
文献类型：
--
作者：
Feletou, M;Jamonneau, I;Canet, E
本研究的目的是评估缓激肽B-2受体在麻醉和机械通气家兔细菌脂多糖（LPS）诱导休克早期（前3小时）中的作用，并确定HOE 140（一种特异性、强效和长效缓激肽B-2受体拮抗剂）是否可以改善两种脓毒性休克小鼠模型的存活率。在家兔中，LPS注射引起与代谢性酸中毒相关的快速低血压。注射LPS后3小时，我们观察到白细胞减少症、血小板减少症和动脉血环GMP中度增加。HOE 140 [1.7 μ mol/kg推注静脉（i. v.）LPS前20分钟]抑制血压下降，但不影响任何其他研究参数。对小鼠进行腹膜内（i. p.）注射LPS，在注射后4天内诱导几乎100%的死亡率。HOE 140（1 mg/kg i. p.）预处理注射LPS前30分钟和注射后4、8和24小时在4天研究期间的任何给定时间都没有改善存活率。小鼠盲肠结扎和穿孔在小于或等于10天内诱导死亡率>90%。HOE 140（1 mg/kg i.v.）盲肠结扎前30 min给予无明显提高存活率。与以前的报告相比，在本研究中，在兔模型的内毒素休克（早期阶段）和两个小鼠模型的脓毒性休克，缓激肽B-2受体的参与似乎是最小的。
The purpose of our work was to evaluate the role of bradykinin B-2 receptors in the early phase (first 3 h) of bacterial lipopolysaccharide (LPS)-induced shock in anesthetized and mechanically ventilated rabbits and to determine if HOE 140, a specific, potent, and long-acting bradykinin B-2-receptor antagonist, could improve survival in two murine models of septic shock. In rabbits, LPS injection induced rapid hypotension associated with metabolic acidosis. Three hours after the injection of LPS, we observed leukopenia, thrombocytopenia, and a moderate increase in arterial blood cyclic GMP. The injection-of HOE 140 [1.7-mu mol/kg bolus intravenously (i.v.) 20 min before LPS] inhibited the decrease in blood pressure, but did not influence any of the other parameters studied. Mice were subjected to intraperitoneal (i.p.) injection of LPS, which induced almost 100% mortality in the 4 days after the injection. Pretreatment with HOE 140 (1 mg/kg i.p.) 30 min before the LPS injection and 4, 8, and 24 h afterward the injection did not improve survival at any given time during the 4 days of the study. Cecal ligation and puncture in mice induced a mortality rate >90% in less than or equal to 10 days. HOE 140 (1 mg/kg i.v.) given 30 min before cecal ligation did not significantly improve the survival rate. In contrast with previous reports, in the present study in a rabbit model of endotoxic shock (early phase) and in two murine models of septic shock, the involvement of bradykinin B-2 receptors appeared to be minimal.