Bertrand C, Geppetti P, Baker J, Petersson G, Piedimonte G, Nadel J A
Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
J Appl Physiol (1985). 1993 May;74(5):2456-61. doi: 10.1152/jappl.1993.74.5.2456.
We used Evans blue dye to assess the effects of bradykinin on vascular extravasation in nasal mucosa of pathogen-free F344 rats. There was a dose-dependent increase in Evans blue extravasation when bradykinin was delivered by topical instillation in the nose (doses, 25-100 nmol). Only the highest intravenous doses (2 and 5 mumol/kg) of bradykinin caused increased extravasation. When bradykinin was delivered by either route, its effect on extravasation was exaggerated by pharmacological inhibition of the enzymes neutral endopeptidase (NEP) and kininase II [angiotensin-converting enzyme (ACE)]. When bradykinin was instilled locally, the effect of NEP inhibition was predominant; when bradykinin was injected intravenously, the effect of ACE inhibition was predominant. The mechanism of extravasation also varied with the mode of bradykinin delivery: when bradykinin was instilled locally in the nose, the selective neurokinin 1 (NK1) receptor antagonist CP-96,345 markedly inhibited the response, whereas it had no effect on Evans blue extravasation when bradykinin was injected intravenously. We conclude that bradykinin causes dose-related increases in Evans blue dye extravasation in the nose and that these effects are exaggerated when NEP and ACE are inhibited. Topically instilled bradykinin causes vascular extravasation to a large extent via NK1 receptor stimulation, thus suggesting a major role for tachykinins released from sensory nerve endings.
我们使用伊文思蓝染料来评估缓激肽对无病原体F344大鼠鼻黏膜血管外渗的影响。当通过鼻腔局部滴注给予缓激肽（剂量为25 - 100 nmol）时，伊文思蓝外渗呈剂量依赖性增加。只有最高的静脉注射剂量（2和5 μmol/kg）的缓激肽会导致外渗增加。当通过任何一种途径给予缓激肽时，其对血管外渗的作用会因中性内肽酶（NEP）和激肽酶II [血管紧张素转换酶（ACE）]的药理学抑制而增强。当局部滴注缓激肽时，NEP抑制的作用占主导；当静脉注射缓激肽时，ACE抑制的作用占主导。血管外渗的机制也因缓激肽给药方式的不同而有所变化：当在鼻腔局部滴注缓激肽时，选择性神经激肽1（NK1）受体拮抗剂CP - 96,345可显著抑制该反应，而当静脉注射缓激肽时，它对伊文思蓝外渗没有影响。我们得出结论，缓激肽会导致鼻腔中伊文思蓝染料外渗呈剂量相关增加，并且当NEP和ACE被抑制时这些作用会增强。局部滴注的缓激肽在很大程度上通过刺激NK1受体引起血管外渗，因此提示感觉神经末梢释放的速激肽起主要作用。
