[Show abstract][Hide abstract] ABSTRACT: Aminopeptidase P (APP) plays an important role in the catabolism of kinins in human plasma, mostly for des-Arg(9)-bradykinin. Impaired degradation of this active bradykinin metabolite was found to be associated with a decreased APP activity in hypertensive patients who experienced angioedema while being treated with angiotensin I-converting enzyme inhibitors. The pathophysiology of hereditary angioedema is presently attributed only to a quantitative/qualitative C1 inhibitor (CI-INH) defect with increased bradykinin release.
In the context of androgen prophylaxis, increased CI-INH function cannot fully explain protection from angioedema attacks alone because of the limited reversion of the CI-INH defects. Therefore we hypothesized that androgen prophylaxis could enhance plasma APP activity.
Patients with hereditary angioedema were investigated for plasma metallopeptidase activities responsible for kinin catabolism (APP, angiotensin I-converting enzyme, and carboxypeptidase N) and for CI-INH function in treated and untreated patients.
APP activity was asymmetrically distributed in untreated patients (n = 147): the mean value was significantly lower than the value in a reference healthy and unmedicated population (n = 116; P < or = .001). Prophylaxis with androgen induced a significant increase in APP activity (P < or = .001), whereas it did not affect the other metallopeptidase activities. In both patient groups, APP activity showed a significant inverse relationship to disease severity (P < or = .001).
In addition to the effect on circulating CI-INH levels, the increase in APP levels brought on by androgens could contribute to a more effective control of the kinin accumulation considered to be responsible for the symptoms of angioedema.
Full-text · Article · Mar 2008 · The Journal of allergy and clinical immunology
[Show abstract][Hide abstract] ABSTRACT: Amniotic fluid embolism is a potentially fatal complication of pregnancy; although several hypotheses have been formulated, the pathophysiology of this condition is not well known. An exaggerated release of bradykinin, which is activated by products of the amniotic fluid that enter the maternal circulation, could explain the symptoms that are present in amniotic fluid embolism. The objective of this study was to assess whether bradykinin is involved in amniotic fluid embolism.
The plasma bradykinin-generating capacity was measured serially in a patient who experienced amniotic fluid embolism.
The plasma bradykinin-generating capacity was found to be very low at the time of the initial clinical manifestations, which were characterized by severe hypotension, cardiorespiratory arrest, and coagulopathy.
This study suggests a potential role for bradykinin release in the pathophysiology of amniotic fluid embolism.
No preview · Article · Nov 2005 · American journal of obstetrics and gynecology