Baraniuk J N, Silver P B, Kaliner M A, Barnes P J
Division of Rheumatology, Immunology and Allergy, Georgetown University, Washington, DC 20007-2197.
Int Arch Allergy Immunol. 1994;103(2):202-8. doi: 10.1159/000236628.
Bradykinin (BK) is known to stimulate vascular permeability by direct actions on vascular B2 receptors, and may stimulate nociceptive sensory nerves that recruit parasympathetic reflexes which induces glandular secretion. Differences in these responses may occur in allergic rhinitis.
The effects of bradykinin (BK) on nasal secretion in vivo were studied by unilateral BK nasal challenge in 8 normal subjects and 6 subjects with severe perennial allergic rhinitis. BK (0, 100, 1,000 nmol) were applied to one nostril (ipsilateral, IL) and saline lavage fluids collected separately from the IL and contralateral (CL) nostrils for analysis of total protein, albumin, glycoconjugates, and lysozyme.
In both groups, BK induced significant dose-dependent IL total protein and albumin secretion, but significantly more total protein and albumin were stimulated in normal than rhinitis subjects after 1,000 nmol BK. Glycoconjugate and lysozyme secretion was not significantly stimulated on either the IL or CL sides in normal subjects. However, in perennial allergic subjects, BK stimulated significant, dose-dependent glycoconjugate and lysozyme secretion on the IL side. Reflex effects were studied on the CL side. Normal subjects did not have significant CL glandular secretion. In contrast, rhinitis subjects secreted significantly higher amounts of total protein and glycoconjugate on the CL side after 1,000 nmol BK. There was no reflex-mediated albumin exudation in either group.
These results indicate that in normal subjects BK stimulates predominantly vascular permeability, and that cholinergic reflexes do not significantly contribute to their BK-induced nasal secretion. In rhinitis subjects, BK again induced albumin exudation, but with less vascular permeability and greater glandular secretion than normal subjects on the challenged side. Only rhinitis subjects demonstrated significant contralateral reflex-mediated glandular secretion, and this response required the highest dose of BK. This suggests that BK is more adept at directly inducing vascular effects than glandular secretion of nociceptive nerve-parasympathetic reflexes. Alterations in BK-induced vascular permeability, glandular secretion, and neural reflexes occur in patients with severe perennial allergic rhinitis, changes suggestive of 'nasal hyperresponsiveness' to BK.
已知缓激肽(BK)通过直接作用于血管B2受体刺激血管通透性,并且可能刺激伤害性感觉神经,进而引发副交感神经反射,导致腺体分泌。这些反应在变应性鼻炎中可能存在差异。
通过对8名正常受试者和6名重度常年性变应性鼻炎受试者进行单侧BK鼻腔激发试验,研究BK对体内鼻分泌物的影响。将BK(0、100、1000 nmol)应用于一侧鼻孔(同侧,IL),并分别从IL和对侧(CL)鼻孔收集盐水灌洗液,以分析总蛋白、白蛋白、糖缀合物和溶菌酶。
在两组中,BK均诱导了显著的剂量依赖性IL总蛋白和白蛋白分泌,但在给予1000 nmol BK后,正常受试者比鼻炎受试者刺激产生的总蛋白和白蛋白显著更多。正常受试者的IL或CL侧糖缀合物和溶菌酶分泌均未受到显著刺激。然而,在常年性变应性鼻炎受试者中,BK在IL侧刺激了显著的剂量依赖性糖缀合物和溶菌酶分泌。在CL侧研究了反射效应。正常受试者CL侧无显著的腺体分泌。相比之下,在给予1000 nmol BK后,鼻炎受试者CL侧分泌的总蛋白和糖缀合物量显著更高。两组均无反射介导的白蛋白渗出。
这些结果表明,在正常受试者中,BK主要刺激血管通透性,胆碱能反射对其BK诱导的鼻分泌物贡献不显著。在鼻炎受试者中,BK再次诱导白蛋白渗出,但与正常受试者相比,激发侧的血管通透性较低,腺体分泌较多。只有鼻炎受试者表现出显著的对侧反射介导的腺体分泌,且这种反应需要最高剂量的BK。这表明BK比伤害性神经-副交感神经反射的腺体分泌更擅长直接诱导血管效应。重度常年性变应性鼻炎患者中发生了BK诱导的血管通透性、腺体分泌和神经反射改变,这些变化提示对BK存在“鼻高反应性”。