Bradykinin and des-Arg(9)-bradykinin metabolic pathways and kinetics of activation of human plasma.
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 x min(-1) x ml(-1). A mathematical model (y = kt(alpha)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-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.
Cyr
M
M
Faculté de Pharmacie, Université de Montréal, Montréal, Canada H3C 3J7.
Lepage
Y
Y
Blais
C
C
Gervais
N
N
Cugno
M
M
Rouleau
J L
JL
Adam
A
A
D000328:Adult; D000368:Aged; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D007705:Kinins / Q000378:metabolism; D001121:Lysine Carboxypeptidase / Q000378:metabolism; D008297:Male; D008666:Metalloendopeptidases / Q000097:blood; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010949:Plasma / Q000502:physiology*
D007705:Kinins; C024626:bradykinin, des-Arg(9)-; D007703:Peptidyl-Dipeptidase A; D001121:Lysine Carboxypeptidase; D008666:Metalloendopeptidases; D001920:Bradykinin