Inhibition of Aminopeptidase P Potentiates Wheal Response to Bradykinin in Angiotensin-Converting Enzyme Inhibitor-Treated Humans
Abstract
Bradykinin is a nonapeptide that contributes to the cardioprotective effects of angiotensin-converting enzyme (ACE) inhibitors. During ACE inhibition, an increased proportion of bradykinin is degraded through non-ACE pathways. Studies in animals suggest that aminopeptidase P (EC 3.4.11.9) may contribute to the metabolism of bradykinin. The purpose of the present study was to determine the contribution of aminopeptidase P to the degradation of bradykinin in humans in the presence and absence of ACE inhibition. To do this, we measured the wheal response to intradermal injection of bradykinin (0, 1, or 10 nicrog) in the presence or absence of intradermal administration of the specific aminopeptidase P inhibitor apstatin (5 or 10 microg) and oral administration of the ACE inhibitor quinapril (10 mg) in six healthy subjects. Both bradykinin (ANOVA; F = 101.18, P <.001) and apstatin alone (F = 7.01, P =.049) caused a wheal of dose-dependent size. There was no significant interaction between apstatin and bradykinin (F = 4.94, P =.175). Pretreatment with 10 mg of quinapril significantly shifted the dose-response curve for bradykinin to the left (effect of quinapril; F = 77.96, P <.001) and there was significant interaction between quinapril and bradykinin (F = 7.82, P =.041). The effect of quinapril was significantly potentiated by coinjection of 10 microg of apstatin (effect of apstatin; F = 21.60, P =.006), such that there was significant interactive effect of quinapril and apstati…
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ACEi patients who received subcutaneous injections of the APP inhibitor Apstatin developed local inflammations.
“One study reported that ACEi patients who received subcutaneous injections of the APP inhibitor Apstatin developed local inflammations (Kim et al. 2000).”
From A variant in XPNPEP2 is associated with angioedema induced by angiotensin I-converting enzyme inhibitors. (2005) · cites this paper as Kim et al. 2000
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Angiotensin-Converting Enzyme Inhibitors
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Self-citationEffect of a new aminopeptidase P inhibitor, apstatin, on bradykinin degradation in the rat lung.
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Aminopeptidase P in individuals with a history of angio-oedema on ACE inhibitors
Adam, A., Cugno, M., Molinaro, G., Perez, M., Lepage, Y., & Agostoni, A. (2002) · The Lancet · doi:10.1016/s0140-6736(02)08914-6 · Cited by 181 · see citing works
Angiotensin-converting enzyme inhibitor-associated angioedema
Byrd, J. B., Adam, A., & Brown, N. J. (2006) · Immunology and Allergy Clinics of North America · doi:10.1016/j.iac.2006.08.001 · Cited by 160 · see citing works
Self-citationCilia La Corte, A. L., Carter, A. M., Rice, G. I., Duan, Q. L., Rouleau, G. A., Adam, A., Grant, P. J., & Hooper, N. M. (2011) · Human Mutation · doi:10.1002/humu.21579 · Cited by 154 · see citing works
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Self-citationDipeptidyl peptidase IV activity in patients with ACE-inhibitor-associated angioedema
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Kinin-dependent hypersensitivity reactions in hemodialysis: metabolic and genetic factors
Molinaro, G., Duan, Q. L., Chagnon, M., Moreau, M. E., Simon, P., Clavel, P., Lavaud, S., Boileau, G., Rouleau, G. A., Lepage, Y., et al. (2006) · Kidney International · doi:10.1038/sj.ki.5001873 · Cited by 29 · see citing works
The bradykinin-degrading aminopeptidase P is increased in women taking the oral contraceptive pill
La Corte, A. L. C., Carter, A. M., Turner, A. J., Grant, P. J., & Hooper, N. M. (2008) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.1177/1470320308096405 · Cited by 21 · see citing works
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- Authors
- Kim, K.-S., Kumar, S., Simmons, W. H., & Brown, N. J.
- Affiliations
- Loyola University Chicago (US)
- Corresponding author
- Brown, Nancy J.
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2000-02
- Volume
- 292
- Issue
- 1
- Pages
- 295-298
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2114202051
- Cited by
- 45
- References
- 2
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2020: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2013: 2 · 2012: 1
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Funders
- National Heart, Lung, and Blood Institute (R29HL056963, HL-56963)
- National Institute of General Medical Sciences (GM-07569, T32GM007569)
- National Center for Research Resources (M01RR000095)
- Topics
- Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pineapple and bromelain studies
- Keywords
- aminopeptidase P, bradykinin, bradykinin degradation, ACE inhibitors, quinapril, skin, drug interactions, cardioprotection, intradermal injection, dose-response curves
- MeSH terms
- Quinapril, Adult, Aminopeptidases, Angiotensin-Converting Enzyme Inhibitors, Bradykinin, Dose-Response Relationship, Drug, Drug Synergism, Female, Humans, Inflammation, Isoquinolines, Male, Peptides, Protease Inhibitors, Time Factors, Urticaria, Tetrahydroisoquinolines
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