Ei. Kalenikova et al., PERINDOPRIL EFFECTS ON ANGIOTENSIN-I ELIMINATION IN LUNG AFTER EXPERIMENTAL MYOCARDIAL INJURY-INDUCED BY INTRACORONARY MICROEMBOLIZATION INRATS, Journal of cardiovascular pharmacology, 32(4), 1998, pp. 608-615
The objective of the study was to determine whether angiotensin (Ang)
I elimination in lung circulation depends on the degree of myocardial
damage with and without early long-term perindopril treatment in a rat
model of myocardial injury induced by intracoronary microembolization
. Twenty-one days after surgery, steady-state arterial [(125)]-Ang I a
nd [(125)]-Ang II blood concentrations were measured after high-perfor
mance liquid chromatography separation during i.v. infusion of [(125)]
-Ang I in three groups of male Wistar conscious rats: (a) sham-operate
d rats receiving saline (sham group, n = 6); (b) rats after coronary m
icroembolization receiving saline (saline group, n = 7); and (c) rats
after coronary microembolization receiving perindopril (2 mg/kg/day; f
rom days 2-20 after embolization; perindopril group, n = 6). Ang I cle
arance and the Ang I-to-Ang II concentration ratio (R) were estimated.
The embolization per se resulted in focal fibrosis, appearance of hyp
ertrophic and dystrophic cardiac myocytes, and was accompanied by incr
eased Ang I clearance (1,479 vs. 314 ml/min in sham group), 1.8-fold d
ecreased [(125)]-Ang II arterial level, and decreased R (0.5 vs. 1.2 i
n sham group; p < 0.05). Only Ang I concentrations and R were correlat
ed with number of scars (r = -0.77; p < 0.05; and r = -0.82; p < 0.01,
respectively). Captopril bolus (1 mg/kg, i.v.) caused similar reducti
on in [(125)]-Ang II blood concentration in both sham and saline group
s, but a significant increase of [(125)]-Ang I blood concentration was
detected in the sham group only. Thus in rats with coronary microembo
lization, a higher proportion of Ang I in lung circulation is eliminat
ed by pathways independent of angiotensin-converting enzyme. In the pe
rindopril group, a reduced number of scars (seven vs. 17 per slice in
the saline group: p < 0.05), density of dystrophic and hypertrophic ca
rdiac myocytes, and increased content of cell glycogen were observed.
It was accompanied by normalized arterial [(125)]-Ang I concentration,
Ang I clearance, and R; [(125)]-Ang II concentration tended to that i
n sham group. Only in the sham and perindopril groups was there signif
icant correlation between Ang r and Ang TT concentrations The clear re
lation between number of scars per slice and R (I = -0.83; p < 0.01) w
as observed in all rats with embolized coronary vessels (saline and pe
rindopril groups together). In conclusion, in this experimental, model
Ang I elimination in the lung circulation was directly related to the
degree of myocardial damage. Early perindopril treatment prevented ma
ladaptive changes in Ang I processing and led to significant reduction
of the undesirable aftereffects of myocardial tissue damage. Our data
demonstrate the cardioprotective action of perindopril based on its b
eneficial influence on the renin-angiotensin system disturbances.