PERINDOPRIL EFFECTS ON ANGIOTENSIN-I ELIMINATION IN LUNG AFTER EXPERIMENTAL MYOCARDIAL INJURY-INDUCED BY INTRACORONARY MICROEMBOLIZATION INRATS

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.