Petersson G, Bacci E, McDonald D M, Nadel J A
Cardiovascular Research Institute, University of California, San Francisco.
J Pharmacol Exp Ther. 1993 Jan;264(1):509-14.
The increase in vascular permeability associated with neurogenic inflammation in the nasal mucosa is mediated by neuropeptides such as substance P released from sensory nerves. Substance P is degraded by the peptidases neutral endopeptidase-24.11 (NEP-24.11) and angiotensin converting enzyme (ACE). In the present study, we used capsaicin to produce neurogenic inflammation in the nasal mucosa of rats, and we examined the effect of inhibition of NEP-24.11 by phosphoramidon, inhibition of ACE by captopril or inhibition of both enzymes by giving both inhibitors. Using as tracers intravenous Evans blue dye to quantify the extravasation and Monastral blue pigment to localize the sites of leakage, we examined the magnitude and distribution of capsaicin-induced plasma extravasation in the nasoturbinates, maxilloturbinates, ethmoidal turbinates and septum. Capsaicin caused a dose-dependent increase in Evans blue extravasation in the naso- and maxilloturbinates but had only a slight effect in the septum. The leaky blood vessels responsible for this plasma extravasation, as manifested by Monastral blue labeling, were most numerous in the naso- and maxilloturbinates, particularly near the front and free borders. After phosphoramidon, the leakage of Monastral blue was more widespread and extended in a more caudal direction. The response to capsaicin was augmented by phosphoramidon alone but not by captopril alone. However, in the presence of phosphoramidon, captopril further augmented the capsaicin-induced extravasation. We conclude that neurogenic inflammation in the rat nasal mucosa is greatest in the naso- and maxilloturbinates and can be modulated by NEP-24.11 and, to a lesser extent, by ACE.
鼻黏膜中与神经源性炎症相关的血管通透性增加是由感觉神经释放的神经肽（如P物质）介导的。P物质可被肽酶中性内肽酶-24.11（NEP-24.11）和血管紧张素转换酶（ACE）降解。在本研究中，我们使用辣椒素在大鼠鼻黏膜中引发神经源性炎症，并研究了磷酰胺抑制NEP-24.11、卡托普利抑制ACE或同时给予两种抑制剂抑制这两种酶的效果。使用静脉注射伊文思蓝染料作为示踪剂来量化血管外渗，并使用莫纳斯特蓝颜料来定位渗漏部位，我们研究了辣椒素诱导的鼻甲、上颌鼻甲、筛鼻甲和鼻中隔血浆外渗的程度和分布。辣椒素导致鼻甲和上颌鼻甲中伊文思蓝外渗呈剂量依赖性增加，但对鼻中隔的影响较小。由莫纳斯特蓝标记显示的导致这种血浆外渗的渗漏血管在鼻甲和上颌鼻甲中最多，尤其是在前端和游离边缘附近。给予磷酰胺后，莫纳斯特蓝的渗漏更广泛，并向更尾侧的方向扩展。单独使用磷酰胺可增强对辣椒素的反应，但单独使用卡托普利则不能。然而，在存在磷酰胺的情况下，卡托普利进一步增强了辣椒素诱导的外渗。我们得出结论，大鼠鼻黏膜中的神经源性炎症在鼻甲和上颌鼻甲中最为严重，并且可以被NEP-24.11调节，在较小程度上也可被ACE调节。
