Hormonal and cardiac effects of converting enzyme inhibition in rat myocardial infarction.
To explain how converting enzyme inhibition could improve the prognosis in cardiac insufficiency, the effect of converting enzyme inhibition (CEI) by S9490-3 (Perindopril) treatment for 2 months (treated infarctions, n = 18) on hormonal plasma variables and the quantitative and qualitative changes in myocardium were studied in an experimental model of left ventricular infarction in rats (untreated infarctions, n = 18) and compared to a sham-operated control group (n = 15). Induction of myocardial infarction was associated with a transient decrease in blood pressure. CEI treatment maintained a lower blood pressure throughout the experimental period. Plasma renin concentration was not significantly increased in the untreated infarct group (155.4 +/- 136.7 ng AI/ml/hr) as compared to the sham-operated group (47.6 +/- 15.9 ng AI/ml/hr). Plasma aldosterone did not change in the three experimental groups. The plasma level of immunoreactive atrial natriuretic factor increased in the untreated infarct group (185 +/- 245 pg/ml) as compared with the control group (76 +/- 40 pg/ml) and was normalized by CEI (66 +/- 60 pg/ml). Body weight was slightly decreased in both treated and untreated infarct groups, whereas the heart weight was significantly increased in the untreated group (1,540 +/- 310 mg) and normalized by treatment (1,145 +/- 180 mg) as compared with sham-operated controls (1,071 +/- 80 mg). The combined atria and right ventricular mass was significantly increased in the untreated infarct group (660 +/- 210 mg) and decreased by treatment (443 +/- 106 mg) but was not completely normalized (controls, 343 +/- 40 mg). Left ventricular isomyosin profiles were modified by myocardial infarction as compared with controls: V1 form decreased from 62.4 +/- 9.4% in the sham-operated group to 41.6 +/- 13.4% in the infarct group, and the V3 form increased from 13.0 +/- 4.7% in sham-operated animals to 27.4 +/- 11.8% in untreated infarct animals. CEI treatment partially, but significantly, reversed this modification of the isomyosin profile (V1, 53.0 +/- 14.4%; V3, 17.5 +/- 8.0%). Volume density of collagen was significantly increased in the untreated infarct rats (4.14 +/- 0.81% versus 2.68 +/- 0.49% in controls), and this was reversed by treatment (2.95 +/- 0.66%). Messenger RNA encoding for atrial natriuretic factor, measured by dot blot hybridization, was significantly increased in both the atria and the ventricles in the untreated infarct group, and treatment by CEI partially reversed this increase. Thus, myocardial infarction profoundly modified several variables of peripheral circulation and quantitative and qualitative myocardial protein expression.(ABSTRACT TRUNCATED AT 400 WORDS)
Michel
J B
JB
INSERM U36, Hôpital Broussais, Paris, France.
Lattion
A L
AL
Salzmann
J L
JL
Cerol
M L
ML
Philippe
M
M
Camilleri
J P
JP
Corvol
P
P
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D001794:Blood Pressure; D001835:Body Weight; D003094:Collagen / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D006728:Hormones / Q000097:blood*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009218:Myosins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000806:Angiotensin-Converting Enzyme Inhibitors; D006728:Hormones; D007527:Isoenzymes; D012333:RNA, Messenger; D009320:Atrial Natriuretic Factor; D003094:Collagen; D009218:Myosins