Changes in paw oedema triggered via bradykinin B1 and B2 receptors in streptozotocin-diabetic rats
Changes in paw oedema triggered via bradykinin B1 and B2 receptors in streptozotocin-diabetic rats
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DOI：
10.1016/s0014-2999(01)00883-4
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发表时间：
2001-03-23
影响因子：
5
通讯作者：
Calixto, JB
中科院分区：
文献类型：
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作者：
Campos, MM;Cabrini, DA;Calixto, JB
本研究观察了缓激肽B-1和B-2受体介导的链脲佐菌素糖尿病大鼠足肿胀。足底内致足肿胀(i.pl.)注射缓激肽或选择性的缓激肽B-2受体激动剂酪氨酸-缓激肽([Tyr(8)]缓激肽)(均为3nmoL/paw)在链脲佐菌素治疗4周后显著减少(34+/-8%和40+/-7%)。在链脲佐菌素作用6周时，当P物质或前列腺素P-2(均为10nmol/paw)引起的足肿胀不变时，对缓激肽B-2受体介导的足肿胀的抑制作用最强(分别为66+/-6%和72+/-2%，分别为缓激肽和[Tyr(8)]缓激肽)。选择性缓激肽B-1受体激动剂[Des-Arg(9)]缓激肽(100nmol/paw)在非糖尿病对照组仅引起轻微的足肿胀。对[Des-Arg(9)]缓激肽的反应在链脲佐菌素治疗8周后显著增强(从0.09+/-0.01升至0.38+/-0.05毫升)，在10周时较弱(0.22+/-0.03毫升)，在12周时恢复到基础值(0.11+/-0.03毫升)。鱼精蛋白锌胰岛素治疗(1-3U/天/7周，S.C.)不能逆转8周时对[Tyr(8)]缓激肽反应的抑制或对[Des-Arg(9)]缓激肽反应的增强。因此，链脲佐菌素诱导的糖尿病导致大鼠对激动素的生氧反应发生了长期的变化，其特征是显著减少了水肿量，包括激活缓激肽B-2受体，并伴随着缓激素B-1受体介导的水肿量的增加。(C)2001年，爱思唯尔科学公司出版。
The present study investigated hind paw oedema mediated by bradykinin B-1 and B-2 receptors in streptozotocin-diabetic rats. Paw oedema induced by intraplantar (i.pl.) injection of bradykinin or the selective bradykinin B-2 receptor agonist, Tyrosines-bradykinin ([Tyr(8)]bradykinin) (both 3 nmol/paw), was significantly reduced at 4 weeks after streptozotocin treatment (34 +/- 8% and 40 +/- 7%). At 6 weeks after streptozotocin, when paw oedema caused by substance P or prostaglandin P-2 (both 10 nmol/paw) was unchanged, inhibition of bradykinin B-2 receptor-mediated oedema was maximal (66 +/- 6% and 72 +/- 2%, for bradykinin and [Tyr(8)]bradykinin, respectively). The selective bradykinin B-1 receptor agonist, [des-Arg(9)]bradykinin (100 nmol/paw), induced only slight paw oedema in non-diabetic controls. Responses to [des-Arg(9)]bradykinin were markedly enhanced 8 weeks after streptozotocin (from 0.09 +/- 0.01 to 0.38 +/- 0.05 ml), less so at 10 weeks (0.22 +/- 0.03 ml), and returning to basal values at 12 weeks (0.11 +/- 0.03 ml). Treatment with insulin protamine zinc (1-3 U/day/7 weeks, s.c.) did not reverse the inhibition of responses to [Tyr(8)]bradykinin or the potentiation of responses to [des-Arg(9)]bradykinin seen at 8 weeks. Thus, streptozotocin-induced diabetes induces long-lasting alterations in oedematogenic responsiveness to kinins in the rat, characterized by marked reduction of oedema involving activation of bradykinin B-2 receptors, associated with enhancement of bradykinin B-1 receptor-mediated oedema. (C) 2001 Published by Elsevier Science B.V.