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

Abstract

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 = ktαe−β 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.