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Kinins IV pp 435-443 | Cite as

Aggregate Anaphylaxis and Carboxypeptidase N

  • James W. Ryan
  • Pierre Berryer
  • Mary Ann Hart
  • Una S. Ryan
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 198A)

Summary

Bradykinin (BK) is widely believed to play a role in the pathogenesis of anaphylaxis. To help clarify any such roles, we examined for effects of inhibitors of kininase II (angiotensin converting enzyme, ACE) and “kininase I” (carboxypeptidase N, CPN), on the early course of egg albumin-induced aggregate anaphylaxis in anesthetized guinea pigs. In this model, pulmonary and systemic arterial blood pressure (BP) rise (unless pulmonary fibrillation occurs), lung wgt increases by ~ 60% and pulmonary microvessels are occluded by cell-rich thrombi, all within 5 min of i. v. antigen. The 30 min mortality rate is ~ 2%. ACE inhibitors (BPP9a, Captopril and MK 422; doses up to 140 μmol/kg) do not make anaphylaxis more nor less severe in terms discernible by changes in BP, lung wgt, EKG or intravascular coagulation. In marked contrast, an inhibitor of CPN (2-mercaptomethyl-3-guanidinoethylthiopropionic acid, 2-MGP; 8–16 μmol/kg) increases the 30 min mortality rate to 94% and lung wgt to 180% of control. The animals die in ventricular fibrillation. Given the enormous BK potentiating effects of BPP9a, Captopril and MK 422, it seems likely that little if any BK is formed in the early min of anaphylaxis. 2-MGP does not potentiate BP effects of BK but markedly potentiates effects of C3a anaphylatoxin. Thus, our data support the views that 1) BK is neither a primary nor secondary mediator of aggregate anaphylaxis, and 2) the adverse effects of 2-MGP are best explained in terms of preservation of anaphylatoxins and not in terms of preservation of kinins.

Keywords

Angiotensin Converting Enzyme Ventricular Fibrillation Antigenic Challenge Insufflation Pressure Chart Speed 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • James W. Ryan
    • 1
  • Pierre Berryer
    • 1
  • Mary Ann Hart
    • 1
  • Una S. Ryan
    • 1
  1. 1.Department of MedicineUniversity of MiamiMiamiUSA

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