The
Effect of Captopril on Nitric Oxide Formation and
on Generation of Radical Forms of Mitochondrial
Respiratory Chain Compounds in Ischemic Rat Heart
H.
VAVŘÍNKOVÁ, M. TUTTEROVÁ, P. STOPKA1,
J. DIVIŠOVÁ,
L. KAZDOVÁ Z. DRAHOTA2
Institute
for Clinical and Experimental Medicine,
1Institute of Inorganic Chemistry, Czech Academy
of Sciences, and 2Institute of Physiology, Czech
Academy of Sciences, Prague, Czech Republic
Received April 22, 2000
Accepted February 14, 2001
Summary
The
increase of radical forms of mitochondrial
respiratory chain compounds (MRCC) is an
indicator of an increased risk of the formation
of oxygen radicals. Using electron paramagnetic
resonance (EPR), we found an increase of signals
corresponding to ubisemichinone radical (·QH)
and ironsulfur proteins radical forms (·FeS) of
these respiratory chain compounds during ischemia
in the isolated perfused rat heart (·QH
increased from 1.51 to 3.08, ·FeS1
from 1.14 to 2.65 arbitrary units). During the
5-min reperfusion, the signals returned to
normoxic levels. In isolated mitochondria exposed
to anoxia and reoxygenation the radical forms of
·QH and ·FeS2 changed in a similar
manner as in the intact heart. A combination of
in vivo captopril treatment and in vitro
L-arginine administration significantly decreased
the levels of MRCC radicals in the isolated
myocardium (·QH from 2.61 to 1.72 and ·FeS1
from 1.82 to 0.46 under normoxia; ·QH from 4.35
to 2.66 and ·FeS1 from 1.93 to 1.35
during ischemia). This decrease in MRCC radical
forms was associated with increased NO levels in
the perfusate, determined as NO2-/ NO3-,
as well as tissue NO levels determined using EPR
as the dinitrosyl iron complex (DNIC). These
results provide new information about the
cardioprotective effects of ACE inhibitors and
L-arginine.
Key
words
ACE
inhibitors · L-arginine · Mitochondrial
radicals · Nitric oxide · Ischemia-reperfusion
injury · Heart ischemia
Reprint
requests
Ing.
Hana Vavřínková, CSc., Department of.
Metabolic Research, IKEM, Vídeňská 1958/9,
Prague 4, 140 21, Czech Republic, fax:
02/61083490, e-mail: havv@medicon.cz
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