Yokoyama T, Tokuyama K, Morikawa A, Kuroume T
Department of Pediatrics, Gunma University School of Medicine, Japan.
Eur J Pharmacol. 1993 Jun 4;236(3):427-32. doi: 10.1016/0014-2999(93)90481-v.
To study the effect of maturation on bradykinin-induced airflow obstruction and airway microvascular leakage, we measured changes in both lung resistance (RL) and extravasation of Evans Blue dye in anaesthetized immature (aged 12 +/- 1 days) and adult guinea-pigs (aged 77 +/- 2 days). After measurement of RL after i.v. administration of bradykinin (2.5, 5 and 10 nmol/kg) or vehicle (0.9% NaCl), dye extravasation in the lower airways was examined in the same animal. Bradykinin did not cause a significant increase in RL in immature airways, whereas even 2.5 nmol/kg induced a significant elevation in adult airways. Bradykinin-induced extravasation of Evans Blue dye was greater in adult than in immature animals. Phosphoramidon (2.5 mg/kg), a neutral endopeptidase inhibitor, did not abolish the age-related difference in the amount of dye extravasated, suggesting that mechanisms other than changes in neutral endopeptidase activity may be responsible for the lower potency of bradykinin in inducing airway microvascular leakage in immature airways.
为研究成熟对缓激肽诱导的气流阻塞和气道微血管渗漏的影响，我们在麻醉的未成熟豚鼠（12±1日龄）和成年豚鼠（77±2日龄）中测量了肺阻力（RL）的变化以及伊文思蓝染料的外渗情况。静脉注射缓激肽（2.5、5和10 nmol/kg）或赋形剂（0.9%氯化钠）后测量RL，然后在同一动物中检查下呼吸道的染料外渗情况。缓激肽未引起未成熟气道RL的显著增加，而即使2.5 nmol/kg也会导致成年气道RL显著升高。缓激肽诱导的伊文思蓝染料外渗在成年动物中比未成熟动物中更明显。磷酰胺（2.5 mg/kg），一种中性内肽酶抑制剂，并不能消除染料外渗量的年龄相关差异，这表明除中性内肽酶活性变化之外的机制可能是缓激肽在诱导未成熟气道微血管渗漏中效力较低的原因。
