Bradykinin and des-Arg(9)-bradykinin metabolic pathways and kinetics of activation of human plasma

Am J Physiol Heart Circ Physiol. 2001 Jul;281(1):H275-83. doi: 10.1152/ajpheart.2001.281.1.H275.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bradykinin / analogs & derivatives*
  • Bradykinin / blood
  • Bradykinin / metabolism*
  • Female
  • Half-Life
  • Humans
  • Kinetics
  • Kinins / metabolism
  • Lysine Carboxypeptidase / metabolism
  • Male
  • Metalloendopeptidases / blood
  • Middle Aged
  • Peptidyl-Dipeptidase A / metabolism
  • Plasma / physiology*

Substances

  • Kinins
  • bradykinin, des-Arg(9)-
  • Peptidyl-Dipeptidase A
  • Lysine Carboxypeptidase
  • Metalloendopeptidases
  • Bradykinin