Des-Arg9-bradykinin metabolism in patients who presented hypersensitivity reactions during hemodialysis:: role of serum ACE and aminopeptidase P

被引:48
作者
Blais, C
Marc-Aurèle, J
Simmons, WH
Loute, G
Thibault, P
Skidgel, RA
Adam, A [1 ]
机构
[1] Univ Montreal, Fac Pharm, Montreal, PQ H3C 3J7, Canada
[2] Hop Sacre Coeur, Montreal, PQ H4J 1C5, Canada
[3] Loyola Univ, Stritch Sch Med, Dept Mol & Cellular Biochem, Maywood, IL 60153 USA
[4] Ctr Hosp St Ode, B-6680 St Ode, Belgium
[5] Conseil Natl Rech Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada
[6] Univ Illinois, Dept Pharmacol, Lab Peptide Res, Coll Med, Chicago, IL 60612 USA
关键词
kinin metabolism; hypersensitivity reactions; hemodialysis; angiotensin-converting enzyme inhibitor; aminopeptidase P;
D O I
10.1016/S0196-9781(99)00020-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 t(1/2) of BK was found between the patient groups. However, the t(1/2) of generated des-Arg(9)-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 t(1/2) of both BK and des-Arg(9)-BK in both groups. There was no significant difference between the groups with respect to the t(1/2) of BK, but there was a significantly greater increase (3.8-fold) in the t(1/2) of des-Arg(9)-BK in HSR+ patients compared to HSR-subject. 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 (r(2) = 0.6271; P < 0.00005) could be calculated between APP activity and des-Arg(9)-BK t(1/2). 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-Arg(9)-BK may lead to the accumulation of this B-1 agonist that could be responsible, at least in part, for the signs and symptoms of HSR. (C) 1999 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:421 / 430
页数:10
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