Serum interspecies differences in the metabolic pathways of
bradykinin (bk) and desarg9-bk: influence of enalaprilat.
D[acute]ecarie, Anick, Philippe Raymond, Nicole Gervais, R[acute]ejean
Couture, and Albert Adam.
D[acute]epartement de physiologie, Facult[acute]e de
m[acute]edecine, Facult[acute]e de pharmacie, Universit[acute]e de
Montr[acute]eal, Montr[acute]eal, Qu[acute]ebec, Canada, H3C 3J7
APStracts 3:0131H, 1996.
Among the different enzymes responsible for the metabolism of
bradykinin (BK), three peptidases look relevant in vivo: kininase I
(KI) which transforms BK into its active metabolite, desArg9-BK,
kininase II (KII) and neutral endopeptidase which inactivate BK and
desArg9-BK. The in vitro incubation of BK and desArg9-BK in the serum
of four species with or without enalaprilat and the quantification of
the immunoreactivity of both peptides at different time intervals
allowed the measurement of the kinetic parameters characterizing
their metabolic pathways. Highly sensitive chemiluminescent enzyme
immunoassays were used to measure the residual concentrations of BK
and desArg9-BK. Half-life (T1/2) of BK showed significant differences
between species: rat (10 +/- 1s) = dog (13 +/- 1s) < rabbit (31
+/- 1s) < human (49 +/- 2s). T1/2 values of desArg9-BK were also
species dependent: rat (96 +/- 6s) << rabbit (314 +/- 6s) =
dog (323 +/- 11s) = human (325 +/- 12s). Enalaprilat significantly
prevented the rapid BK and desArg9-BK degradation in all species
except that of desArg9-BK in the rat serum. The relative amount of BK
hydrolysed by serum KII was given as follows: rabbit (93.7 +/- 14.8%)
= rat (83.6 +/- 6.7%) = human (76.0 +/- 7.5%) > dog (50.0 +/-
3.9%). Its importance in the hydrolysis of desArg9-BK was 5.2 +/-
0.5% in rat << 33.9 +/- 1.5% in human < 52.0 +/- 1.1%
in rabbit < 65.1 +/- 3.4% in dog. The participation of serum KI
in the transformation of BK into desArg9-BK was: dog (67.2 +/- 5.3%)
>> human (3.4 +/- 1.2%) = rabbit (1.8 +/- 0.2%) = rat (1.4
+/- 0.3%). Finally, no significant difference on T1/2 values for BK
and desArg9-BK could be demonstrated between serum and plasma treated
with either sodium citrate or a thrombin inhibitor. These results
revealed striking species differences in the serum metabolism of
kinins that could address at least partially some of the
controversial data related to the cardioprotective role of kinins.
Received 5 October 1995; accepted in final form 25 March 1996.
APS Manuscript Number H942-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 1 April 96