Jaffa A A, Pratt J, Ashford A, Bailey G S
Adv Exp Med Biol. 1986;198 Pt B:373-8. doi: 10.1007/978-1-4757-0154-8_47.
Infusion of bradykinin (1 microgram/min) or saline vehicle for 30 minutes into alloxan-diabetic rats produced no change in the very high levels of blood glucose. Furthermore, intravenous injection of captopril (3 mg/Kg body weight) into the diabetic rats did not result in a significant change of glucose concentrations over a period of 60 minutes. However, infusion of bradykinin 15 minutes after intravenous injection of captopril resulted in a marked decrease of glucose levels (p less than 0.01, compared to pretreatment) by 20 minutes after the start of the infusion. Thus, the captopril potentiated the effect of the kinin, possibly by inhibition of kininase II. Using a spectrophotometric assay with Bz-Gly-Gly-Gly as substrate insulin was shown to be an inhibitor of kininase II purified from hog lungs with an I50 of 1.6 X 10(-5)M compared to captopril with I50 of 2.2 X 10(-9)M. Furthermore, it was found that in vivo infusion of as little as 50 mU insulin over a period of 30 minutes, a dose that by itself was ineffective, potentiated the glucose-lowering activity of a bradykinin infusion in alloxanized rats. Interestingly, the infusion of insulin 15 minutes after injection of captopril, at doses of each compound which alone were inactive, did produce a significant fall (p less than 0.005) in glucose concentrations. Overall, the results show that captopril, insulin and bradykinin can interact to promote a reduction in blood glucose of alloxan-diabetic rats.
向四氧嘧啶糖尿病大鼠输注缓激肽（1微克/分钟）或生理盐水载体30分钟，对极高的血糖水平没有影响。此外，给糖尿病大鼠静脉注射卡托普利（3毫克/千克体重），在60分钟内血糖浓度没有显著变化。然而，在静脉注射卡托普利15分钟后输注缓激肽，输注开始20分钟后血糖水平显著下降（与预处理相比，p小于0.01）。因此，卡托普利可能通过抑制激肽酶II增强了激肽的作用。使用以Bz-Gly-Gly-Gly为底物的分光光度法测定，结果显示胰岛素是从猪肺中纯化的激肽酶II的抑制剂，其半数抑制浓度（I50）为1.6×10⁻⁵M，而卡托普利的I50为2.2×10⁻⁹M。此外，还发现，在四氧嘧啶处理的大鼠中，在30分钟内输注低至50 mU胰岛素（该剂量本身无效）可增强缓激肽输注的降血糖活性。有趣的是，在注射卡托普利15分钟后输注胰岛素，单独使用时每种化合物均无活性，但确实使血糖浓度显著下降（p小于0.005）。总体而言，结果表明卡托普利、胰岛素和缓激肽可以相互作用，促进四氧嘧啶糖尿病大鼠的血糖降低。
