Schaffel R, Rodrigues M S, Assreuy J
Department of Pharmacology, ICB/CCS, Universidade Federal do Rio de Janeiro.
Can J Physiol Pharmacol. 1991 Jul;69(7):904-8. doi: 10.1139/y91-137.
Prolongation of bradykinin half-life following kininase inhibition has been proposed as the reason for the potentiation of kinin effects. We have reassessed this assumption by using three different isolated smooth muscle preparations and simultaneously studying the inhibition of kininase activity and the potentiation of bradykinin effects by enalaprilat and BPP9a. Rat duodenum displayed higher total kininase activity, metabolizing half of the added bradykinin in 6.5 min, while this time for rat uterus was greater than 60 min. Guinea-pig ileum showed the intermediate value of 14.6 min. Enalaprilat and BPP9a slowed the metabolism of bradykinin by 50-100% in rat duodenum and by 50-180% in guinea-pig ileum, showing that a significant fraction of total kininase activity appears to be due to kininase II. In rat duodenum, an almost complete blockade of kininase activity was achieved when bacitracin and mergetpa were used together with enalaprilat. Enalaprilat and BPP9a potentiated bradykinin effects in guinea-pig ileum and rat uterus. In contrast, bradykinin-induced relaxations and contractions in rat duodenum were not potentiated by enalaprilat, BPP9a, or by the enzyme inhibitor mixture (enalaprilat--bacitracin--mergetpa). The results suggest that inhibition of bradykinin enzymatic metabolism by kininases does not necessarily lead to the potentiation of bradykinin effects.
激肽酶抑制后缓激肽半衰期的延长被认为是激肽作用增强的原因。我们通过使用三种不同的离体平滑肌制剂，并同时研究依那普利拉和BPP9a对激肽酶活性的抑制作用以及对缓激肽作用的增强作用，重新评估了这一假设。大鼠十二指肠显示出较高的总激肽酶活性，在6.5分钟内代谢掉一半添加的缓激肽，而大鼠子宫的这个时间大于60分钟。豚鼠回肠显示出中间值14.6分钟。依那普利拉和BPP9a使大鼠十二指肠中缓激肽的代谢减慢50 - 100%，使豚鼠回肠中缓激肽的代谢减慢50 - 180%，表明总激肽酶活性的很大一部分似乎归因于激肽酶II。在大鼠十二指肠中，当杆菌肽和mergetpa与依那普利拉一起使用时，激肽酶活性几乎完全被阻断。依那普利拉和BPP9a增强了豚鼠回肠和大鼠子宫中缓激肽的作用。相比之下，依那普利拉、BPP9a或酶抑制剂混合物（依那普利拉 - 杆菌肽 - mergetpa）并未增强缓激肽在大鼠十二指肠中诱导的舒张和收缩。结果表明，激肽酶对缓激肽酶促代谢的抑制不一定会导致缓激肽作用的增强。
