血管性水肿中的血浆缓激肽。

Plasma bradykinin in angio-oedema.

作者信息

Nussberger J, Cugno M, Amstutz C, Cicardi M, Pellacani A, Agostoni A

机构信息

Hypertension Division, University Hospital Lausanne, Switzerland.

出版信息

Lancet. 1998 Jun 6;351(9117):1693-7. doi: 10.1016/S0140-6736(97)09137-X.

DOI:10.1016/S0140-6736(97)09137-X

PMID:9734886

Abstract

BACKGROUND

Bradykinin is believed to be the main mediator of symptoms in hereditary (HA) and acquired (AA) angio-oedema due to C1 esterase inhibitor deficiency, as well as in angio-oedema that complicates treatment with inhibitors of angiotensin-converting enzyme (ACE). Difficulties in the measurement of kinin concentrations, however, have so far precluded the demonstration of an incontrovertible change in plasma bradykinin concentrations in these disorders. By developing a reliable assay we have been able to follow bradykinin concentrations during attacks and during remission in HA and in AA, and also in a patient treated with an ACE-inhibitor.

METHODS

Liquid-phase extraction, high-performance liquid chromatography, and RIA were used for specific measurement of plasma bradykinin concentrations in 22 patients with HA and in 22 healthy volunteers of similar age and sex distribution. Four patients with AA and one hypertensive patient treated with the ACE inhibitor captopril were also studied.

FINDINGS

Among the healthy volunteers plasma bradykinin concentration was inversely proportional to age. The geometric mean plasma bradykinin concentration in the healthy volunteers was 2.2 fmol/mL (SD 2.2), compared with 3.9 fmol/mL (3.7) among patients with HA during remission (p=0.095). Bradykinin was also high in the patients with AA (10.4 fmol/mL [1.6]). During acute attacks of oedema, in both HA and AA, plasma bradykinin rose to two to 12 times the upper limit of normal. Infusion of C1-esterase inhibitor (the deficient factor in both HA and AA) immediately lowered bradykinin concentrations. In the patient receiving the ACE-inhibitor captopril, bradykinin concentration was very high at 47 fmol/mL during an acute attack of angio-oedema, but normal at 3.2 fmol/mL in remission after withdrawal of the drug.

INTERPRETATION

A sensitive method for measurement of plasma bradykinin provided the means to show that concentrations of this peptide decrease with age in healthy people. Although the differences between patients in remission and healthy controls did not reach statistical significance, there were substantial rises in bradykinin during acute attacks of hereditary, acquired, or captopril-induced angio-oedema.

摘要

背景

缓激肽被认为是遗传性（HA）和获得性（AA）血管性水肿（由于C1酯酶抑制剂缺乏所致）以及血管紧张素转换酶（ACE）抑制剂治疗引起的并发症血管性水肿症状的主要介质。然而，由于激肽浓度测量存在困难，迄今为止尚未证实这些疾病中血浆缓激肽浓度有确凿的变化。通过开发一种可靠的检测方法，我们得以追踪HA和AA发作期及缓解期的缓激肽浓度，以及一名接受ACE抑制剂治疗患者的缓激肽浓度。

方法

采用液相萃取、高效液相色谱和放射免疫分析法，对22例HA患者和22名年龄及性别分布相似的健康志愿者的血浆缓激肽浓度进行特异性检测。还对4例AA患者和1例接受ACE抑制剂卡托普利治疗的高血压患者进行了研究。

结果

在健康志愿者中，血浆缓激肽浓度与年龄呈反比。健康志愿者的血浆缓激肽几何平均浓度为2.2 fmol/mL（标准差2.2），而HA患者缓解期为3.9 fmol/mL（3.7）（p = 0.095）。AA患者的缓激肽水平也较高（10.4 fmol/mL [1.6]）。在HA和AA的急性水肿发作期，血浆缓激肽升高至正常上限的2至12倍。输注C1酯酶抑制剂（HA和AA中均缺乏的因子）可立即降低缓激肽浓度。在接受ACE抑制剂卡托普利治疗的患者中，血管性水肿急性发作时缓激肽浓度非常高，达47 fmol/mL，但停药缓解期正常，为3.2 fmol/mL。