Rajakulasingam K, Polosa R, Lau L C, Church M K, Holgate S T, Howarth P H
Immunopharmacology Group, Southampton General Hospital.
Thorax. 1993 Apr;48(4):324-9. doi: 10.1136/thx.48.4.324.
Bradykinin may contribute to the pathogenesis of allergic rhinitis. Like histamine, nasal challenge with bradykinin induces rhinorrhoea, nasal blockage, and plasma protein leakage. Their comparative nasal potencies have not, however, been fully elucidated.
Three double blind, randomised, placebo controlled and cross-over studies were undertaken to compare objectively the nasal effects of bradykinin, histamine, and vehicle.
Both bradykinin and histamine produced dose dependent increases in nasal airways resistance (NAR). There was no significant difference in the effects of bradykinin and histamine on NAR at any dose level. On a molar basis, however, bradykinin was 6.98 times more potent than histamine in inducing a 50% increase in NAR. Nasal challenge with bradykinin and histamine also induced significant rhinorrhoea compared with vehicle. The amount of rhinorrhoea induced by histamine was significantly greater than that induced by bradykinin at any dose level. Bradykinin and histamine induced dose dependent nasal pain and nasal itch respectively. When administered as single doses both bradykinin (1.9 mumol) and histamine (1.9 mumol) induced significant rhinorrhoea compared with the vehicle. The volume of rhinorrhoea secretions induced by histamine was 29% greater than that induced by bradykinin. In contrast, although NAR was increased significantly more by histamine than by the vehicle, the effect of bradykinin on NAR was significantly greater than histamine and vehicle in both magnitude and duration of effect. The incremental effect of bradykinin on lavage albumin levels was also significantly greater than both histamine and vehicle.
This study shows that the nasal vascular effects of histamine are less prominent than its actions on rhinorrhoea, and that the greater obstructive effect of bradykinin than histamine on NAR may contribute to the relative lack of efficacy of H1 antihistamines on nasal blockage in clinical disease.
缓激肽可能参与过敏性鼻炎的发病机制。与组胺一样，用缓激肽进行鼻腔激发可诱发鼻漏、鼻塞和血浆蛋白渗漏。然而，它们相对的鼻腔效价尚未完全阐明。
进行了三项双盲、随机、安慰剂对照和交叉研究，以客观比较缓激肽、组胺和赋形剂的鼻腔效应。
缓激肽和组胺均使鼻气道阻力（NAR）呈剂量依赖性增加。在任何剂量水平下，缓激肽和组胺对NAR的影响均无显著差异。然而，以摩尔为基础，缓激肽在诱导NAR增加50%方面的效价比组胺高6.98倍。与赋形剂相比，用缓激肽和组胺进行鼻腔激发也可诱发显著的鼻漏。在任何剂量水平下，组胺诱发的鼻漏量均显著大于缓激肽诱发的鼻漏量。缓激肽和组胺分别诱发剂量依赖性的鼻痛和鼻痒。当单剂量给药时，与赋形剂相比，缓激肽（1.9 μmol）和组胺（1.9 μmol）均诱发显著的鼻漏。组胺诱发的鼻漏分泌量比缓激肽诱发的鼻漏分泌量多29%。相比之下，尽管组胺使NAR增加的幅度明显大于赋形剂，但缓激肽对NAR的影响在作用幅度和持续时间上均明显大于组胺和赋形剂。缓激肽对灌洗白蛋白水平的增量效应也明显大于组胺和赋形剂。
本研究表明，组胺的鼻腔血管效应不如其对鼻漏的作用突出，并且缓激肽对NAR的阻塞作用比组胺更强，这可能导致H1抗组胺药在临床疾病中对鼻塞的疗效相对不足。
