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-lif e (27 +/- 10 s) was lower than that of des-Arg(9)-BK (643 +/- 436 s) and wa s statistically different in men compared with women. The potentiating effe ct of an angiotensin-converting enzyme (ACE) inhibitor was, however, more e xtensive for BK (9.0-fold) than for des-Arg(9)-BK (2.2-fold). The activitie s of ACE, aminopeptidase P (APP), and kininase I were respectively 44 +/- 1 2, 22 +/- 9, and 62 +/- 10 nmol.min(-1).ml(-1). A mathematical model (y = k t(alpha)e(-betat), t > 0), applied to the BK kinetically released from endo genous high-molecular-weight kininogen (HK) during plasma activation in the presence of an ACE inhibitor, revealed a significant difference in the rat e of formation of BK between men and women. For des-Arg(9)-BK, the active m etabolite 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 pathophys iological studies of inflammatory processes where activation of the contact system of plasma and the kinins is involved.