Abstract |
Bradykinin (BK) has been proposed as the principal mediator of hypersensitivity reactions (HSR) in patients dialyzed using negatively charged membranes and concomitantly treated with angiotensin-converting enzyme ( ACE) inhibitors. We investigated the metabolism of exogenous BK added to the sera of 13 patients dialyzed on an AN69 membrane with a history of HSR (HSR+ patients) and 10 others who did not present such a reaction (HSR- patients) while dialyzed under the same conditions. No significant difference in the t1/2 of BK was found between the patient groups. However, the t1/2 of generated des-Arg9-BK was significantly increased (2.2-fold) in HSR+ patients compared to HSR-subjects. Preincubation of the sera with an ACE inhibitor ( enalaprilat) significantly increased the t1/2 of both BK and des-Arg9-BK in both groups. There was no significant difference between the groups with respect to the t1/2 of BK, but there was a significantly greater increase (3.8-fold) in the t1/2 of des-Arg9-BK in HSR+ patients compared to HSR-subjects. The level of serum aminopeptidase P (APP) activity showed a significant decrease in the HSR+ sera when compared to HSR-samples. In HSR- and HSR+ patients, a significant inverse relation (r2 = 0.6271; P < 0.00005) could be calculated between APP activity and des-Arg9-BK t1/2. In conclusion, HSR in hemodialyzed patients who are concomitantly treated with a negatively charged membrane and an ACE inhibitor can be considered as a multifactorial disease in that a decreased APP activity resulting in reduced degradation of des-Arg9-BK may lead to the accumulation of this B1 agonist that could be responsible, at least in part, for the signs and symptoms of HSR.
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Authors | C Blais Jr, J Marc-Aurèle, W H Simmons, G Loute, P Thibault, R A Skidgel, A Adam |
Journal | Peptides
(Peptides)
Vol. 20
Issue 4
Pg. 421-30
( 1999)
ISSN: 0196-9781 [Print] United States |
PMID | 10458510
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Acrylic Resins
- Angiotensin-Converting Enzyme Inhibitors
- Membranes, Artificial
- Receptor, Bradykinin B1
- Receptors, Bradykinin
- bradykinin, des-Arg(9)-
- AN-69
- Aminopeptidases
- X-Pro aminopeptidase
- Peptidyl-Dipeptidase A
- Lysine Carboxypeptidase
- Enalaprilat
- Acrylonitrile
- Bradykinin
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Topics |
- Acrylic Resins
- Acrylonitrile
(analogs & derivatives)
- Aged
- Aminopeptidases
(blood)
- Angiotensin-Converting Enzyme Inhibitors
(adverse effects)
- Bradykinin
(analogs & derivatives, pharmacokinetics, pharmacology)
- Enalaprilat
(adverse effects)
- Female
- Humans
- Hypersensitivity
(drug therapy, metabolism)
- Lysine Carboxypeptidase
(metabolism)
- Male
- Membranes, Artificial
- Middle Aged
- Peptidyl-Dipeptidase A
(blood)
- Receptor, Bradykinin B1
- Receptors, Bradykinin
(agonists)
- Renal Dialysis
(adverse effects)
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