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Faculties of 1 Pharmacy,
3 Arts and Sciences, and
4 Medicine,
The respective role of angiotensin-converting
enzyme (ACE) and neutral endopeptidase 24.11 (NEP) in the degradation
of bradykinin (BK) has been studied in the infarcted and hypertrophied
rat heart. Myocardial infarction (MI) was induced in rats by left
descendant coronary artery ligature. Animals were killed, and hearts
were sampled 1, 4, and 35 days post-MI. BK metabolism was assessed by
incubating synthetic BK with heart membranes from sham hearts and
infarcted (scar) and noninfarcted regions of infarcted hearts. The
half-life
(t1/2)
of BK showed significant differences among the three types of tissue at
4 days [sham heart (114 ± 7 s) > noninfarcted region (85 ± 4 s) > infarcted region (28 ± 2 s)] and 35 days
post-MI [sham heart (143 ± 6 s) = noninfarcted region (137 ± 9 s) > infarcted region (55 ± 4 s)]. No difference was observed at 1 day post-MI. The participation of ACE and NEP in the
metabolism of BK was defined by preincubation of the membrane preparations with enalaprilat, an ACE inhibitor, and omapatrilat, a
vasopeptidase inhibitor that acts by combined inhibition of NEP and
ACE. Enalaprilat significantly prevented the rapid degradation of BK in
every tissue type and at every sampling time. Moreover, omapatrilat
significantly increased the
t1/2 of BK
compared with enalaprilat in every tissue type and at every sampling
time. These results demonstrate that experimental MI followed by left ventricular dysfunction significantly modifies the metabolism of
exogenous BK by heart membranes. ACE and NEP participate in the
degradation of BK since both enalaprilat and omapatrilat have potentiating effects on the
t1/2 of BK.
angiotensin-converting enzyme; vasopeptidase inhibitor; left ventricular hypertrophy
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