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Am J Physiol Heart Circ Physiol 281: H275-H283, 2001;
0363-6135/01 $5.00
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Vol. 281, Issue 1, H275-H283, July 2001

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

Mélanie Cyr1, Yves Lepage2, Charles Blais Jr.1, Nicole Gervais1, Massimo Cugno3, Jean-Lucien Rouleau4, and Albert Adam1

1 Faculté de Pharmacie, 2 Faculté des Arts et des Sciences, Département de Mathématiques et Statistique, Université de Montréal, Montréal, Canada H3C 3J7; 3 Department of Internal Medicine, University of Milan, Milano 20122 Italy; and 4 University Health Network, Toronto General Hospital, Toronto, Canada, M5G 2C4

In the serum of 116 healthy individuals, exogenous bradykinin (BK) half-life (27 ± 10 s) was lower than that of des-Arg9-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-Arg9-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 = ktalpha e-beta t, 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-Arg9-BK, the active metabolite of BK, the rate of degradation was higher in women compared with men, correlating significantly with serum APP activity (r2 = 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.

kinins; angiotensin-converting enzyme inhibitors; contact system activation


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