Bradykinin and des-Arg9-bradykinin metabolic pathways and kinetics of activation of human plasma

被引:147
作者
Cyr, M
Lepage, Y
Blais, C
Gervais, N
Cugno, M
Rouleau, JL
Adam, A
机构
[1] Univ Montreal, Fac Pharm, Montreal, PQ H3C 3J7, Canada
[2] Univ Montreal, Fac Arts & Sci, Dept Math & Stat, Montreal, PQ H3C 3J7, Canada
[3] Univ Milan, Dept Internal Med, I-20122 Milan, Italy
[4] Toronto Gen Hosp, Univ Hlth Network, Toronto, ON M5G 2C4, Canada
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2001年 / 281卷 / 01期
关键词
kinins; angiotensin-converting enzyme inhibitors; contact system activation;
D O I
10.1152/ajpheart.2001.281.1.H275
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In the serum of 116 healthy individuals, exogenous bradykinin (BK) half-life (27 +/- 10 s) was lower than that of des-Arg(9)-BK (643 +/- 436 s) and was statistically different in men compared with women. The potentiating effect of an angiotensin-converting enzyme (ACE) inhibitor was, however, more extensive for BK (9.0-fold) than for des-Arg(9)-BK (2.2-fold). The activities of ACE, aminopeptidase P (APP), and kininase I were respectively 44 +/- 12, 22 +/- 9, and 62 +/- 10 nmol.min(-1).ml(-1). A mathematical model (y = kt(alpha)e(-betat), t > 0), applied to the BK kinetically released from endogenous high-molecular-weight kininogen (HK) during plasma activation in the presence of an ACE inhibitor, revealed a significant difference in the rate of formation of BK between men and women. For des-Arg(9)-BK, the active metabolite of BK, the rate of degradation was higher in women compared with men, correlating significantly with serum APP activity (r(2) = 0.6485, P< 0.001). In conclusion, these results constitute a basis for future pathophysiological studies of inflammatory processes where activation of the contact system of plasma and the kinins is involved.
引用
收藏
页码:H275 / H283
页数:9
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