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

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 281; no. 1; p. H275
• Main Authors: Cyr, Melanie, Lepage, Yves, Blais, Charles, Jr, Gervais, Nicole, Cugno, Massimo, Rouleau, Jean-Lucien, Adam, Albert
• Format: Journal Article
• Language: English
• Published: 01.07.2001
• ISSN: 0363-6135; 1522-1539

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-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 e 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-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. kinins; angiotensin-converting enzyme inhibitors; contact system activation