Perindopril effects on angiotensin I elimination in lung after experimental myocardial injury induced by intracoronary microembolization in rats.
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 [125I]-Ang I and [125I]-Ang II blood concentrations were measured after high-performance liquid chromatography separation during i.v. infusion of [125I]-Ang I in three groups of male Wistar conscious rats: (a) sham-operated rats receiving saline (sham group, n = 6); (b) rats after coronary microembolization receiving saline (saline group, n = 7); and (c) rats after coronary microembolization receiving perindopril (2 mg/kg/day; from days 2-20 after embolization; perindopril group, n = 6). Ang I clearance and the Ang I-to-Ang II concentration ratio (R) were estimated. The embolization per se resulted in focal fibrosis, appearance of hypertrophic and dystrophic cardiac myocytes, and was accompanied by increased Ang I clearance (1,479 vs. 314 ml/min in sham group), 1.8-fold decreased [125I]-Ang II arterial level, and decreased R (0.5 vs. 1.2 in sham group; p < 0.05). Only Ang I concentrations and R were correlated 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 reduction in [125I]-Ang II blood concentration in both sham and saline groups, but a significant increase of [125I]-Ang I blood concentration was detected in the sham group only. Thus in rats with coronary microembolization, a higher proportion of Ang I in lung circulation is eliminated by pathways independent of angiotensin-converting enzyme. In the perindopril group, a reduced number of scars (seven vs. 17 per slice in the saline group; p < 0.05), density of dystrophic and hypertrophic cardiac myocytes, and increased content of cell glycogen were observed. It was accompanied by normalized arterial [125I]-Ang I concentration, Ang I clearance, and R; [125I]-Ang II concentration tended to that in sham group. Only in the sham and perindopril groups was there significant correlation between Ang I and Ang II concentrations. The clear relation between number of scars per slice and R (r = -0.83; p < 0.01) was observed in all rats with embolized coronary vessels (saline and perindopril 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 maladaptive 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 beneficial influence on the renin-angiotensin system disturbances.
Cardiology Research Center, Moscow State University, Russia.
E I
EI
Kalenikova
E A
EA
Gorodetskaya
N V
NV
Zacharova
A B
AB
Shechter
O S
OS
Medvedev
D000803:Angiotensin I / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism; D000804:Angiotensin II / Q000097:blood* / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D006439:Hemodynamics / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008863:Microspheres; D020913:Perindopril; D051381:Rats; D017208:Rats, Wistar
D000959:Antihypertensive Agents; D007211:Indoles; D000804:Angiotensin II; D000803:Angiotensin I; D020913:Perindopril