Shore S A, Martins M A, Drazen J M
Respiratory Biology Program, Harvard School of Public Health, Boston, Massachusetts 02115.
Pulm Pharmacol. 1993 Sep;6(3):193-9. doi: 10.1006/pulp.1993.1026.
In order to examine the role of peptidases in modulating bronchoconstrictor responses to i.v. administered capsaicin, a potent C-fiber stimulant, we measured changes in pulmonary conductance (GL) and dynamic compliance (Cdyn) in anesthetized mechanically ventilated guinea-pigs. Control guinea-pigs, and guinea-pigs treated with the neutral endopeptidase (NEP) inhibitors thiorphan (1.7 mg/kg) or SCH32615 (1 mg/kg), the angiotensin converting enzyme (ACE) inhibitor captopril (5.7 mg/kg), or combinations of NEP and ACE inhibitors, were given increasing doses of capsaicin by rapid i.v. injection. The doses of capsaicin required to cause a 50% decrease in GL and Cdyn (ED50GL and ED50Cdyn respectively) were computed for each animal. None of the peptidase inhibitors, when given alone, had any effect on the changes in pulmonary mechanics induced by capsaicin. However, combined administration of thiorphan and captopril, or SCH32615 and captopril, caused a decrease in ED50Cdyn for capsaicin, and prolonged the time during which the peak changes in GL induced by capsaicin persisted. These data support the hypothesis that substances whose degradation is inhibited by combined NEP and ACE inhibitors contribute to the bronchoconstriction induced by iv administered capsaicin. This profile of enzymatic degradation is consistent with the tachykinin, substance P.
为了研究肽酶在调节静脉注射辣椒素（一种有效的C纤维刺激剂）引起的支气管收缩反应中的作用，我们在麻醉状态下机械通气的豚鼠中测量了肺电导（GL）和动态顺应性（Cdyn）的变化。给对照豚鼠以及用中性内肽酶（NEP）抑制剂硫磷酰胺（1.7mg/kg）或SCH32615（1mg/kg）、血管紧张素转换酶（ACE）抑制剂卡托普利（5.7mg/kg）或NEP与ACE抑制剂组合处理的豚鼠通过快速静脉注射给予递增剂量的辣椒素。计算每只动物引起GL和Cdyn降低50%所需的辣椒素剂量（分别为ED50GL和ED50Cdyn）。单独给予时，没有一种肽酶抑制剂对辣椒素引起的肺力学变化有任何影响。然而，硫磷酰胺与卡托普利或SCH32615与卡托普利联合给药导致辣椒素的ED50Cdyn降低，并延长了辣椒素引起的GL峰值变化持续的时间。这些数据支持以下假设：其降解受到NEP和ACE抑制剂联合抑制的物质促成了静脉注射辣椒素引起的支气管收缩。这种酶促降解模式与速激肽P物质一致。
