Morimoto H, Yamashita M, Matsuda A, Ohori M, Miyake H, Fujii T
Department of Pharmacology, Fujisawa Pharmaceutical Co., Ltd, Osaka, Japan.
Jpn J Pharmacol. 1996 Nov;72(3):217-21. doi: 10.1254/jjp.72.217.
We examined the effect of dextran sulfate on guinea pig tracheal vascular permeability. I.v. injection of dextran sulfate (10-100 mg/kg) with captopril (1 mg/kg) induced guinea pig tracheal plasma extravasation. The i.v. administration of bradykinin (0.8-8 micrograms/kg) with captopril (1 mg/kg) also induced plasma extravasation. Bradykinin B2 antagonists, D-Arg[Hyp3-Thi5-D-Tic7-Tic8]-bradykinin (NPC 16731) and D-Arg[Hyp3-Thi5-D-Tic7-Oic8]-bradykinin (Hoe 140), reduced both dextran sulfate (32 mg/kg)- and bradykinin (2.5 micrograms/kg)-induced tracheal plasma extravasation in a dose-dependent manner. However, a cyclooxygenase inhibitor, indomethacin (1 mg/kg), and a neurokinin antagonist, [N-[N2-[N-[N-[N-[2,3-didehydro-N-methyl-N-[N-[3-(2-pentylphenyl )- propionyl]-L-threonyl]tyrosyl-L-leucynyl]-D-phenylalanyl]-L-a llo-threonyl]-L-asparaginyl]-L-serine-D-lactone] (FK 224) (1 mg/kg), had no effect on tracheal plasma extravasation induced by dextran sulfate and bradykinin. Dextran sulfate (32 mg/kg) with captopril (1 mg/kg) greatly increased the bradykinin level in guinea pig plasma. This evidence suggests that dextran sulfate releases bradykinin in guinea pig plasma and causes guinea pig tracheal plasma extravasation via the activation of bradykinin B2-receptors.
我们研究了硫酸葡聚糖对豚鼠气管血管通透性的影响。静脉注射硫酸葡聚糖（10 - 100毫克/千克）与卡托普利（1毫克/千克）可诱导豚鼠气管血浆渗出。静脉注射缓激肽（0.8 - 8微克/千克）与卡托普利（1毫克/千克）也可诱导血浆渗出。缓激肽B2拮抗剂，D - Arg[Hyp3 - Thi5 - D - Tic7 - Tic8] - 缓激肽（NPC 16731）和D - Arg[Hyp3 - Thi5 - D - Tic7 - Oic8] - 缓激肽（Hoe 140），以剂量依赖的方式降低了硫酸葡聚糖（32毫克/千克）和缓激肽（2.5微克/千克）诱导的气管血浆渗出。然而，环氧化酶抑制剂吲哚美辛（1毫克/千克）和神经激肽拮抗剂，[N - [N2 - [N - [N - [N - [2,3 - 二脱氢 - N - 甲基 - N - [N - [3 - （2 - 戊基苯基） - 丙酰基] - L - 苏氨酰基]酪氨酰 - L - 亮氨酰基] - D - 苯丙氨酰基] - L - 别苏氨酰基] - L - 天冬氨酰基] - L - 丝氨酸 - D - 内酯]（FK 224）（1毫克/千克），对硫酸葡聚糖和缓激肽诱导的气管血浆渗出没有影响。硫酸葡聚糖（32毫克/千克）与卡托普利（1毫克/千克）极大地提高了豚鼠血浆中的缓激肽水平。这一证据表明，硫酸葡聚糖在豚鼠血浆中释放缓激肽，并通过激活缓激肽B2受体导致豚鼠气管血浆渗出。
