Comparative effects of angiotensin converting enzyme inhibition (perindopril) or diuretic therapy on cardiac hypertrophy and sympathetic activity following myocardial infarction in rats.
The long-term effects of perindopril or chlorothiazide therapy were studied in rats after the induction of myocardial infarction by coronary artery ligation. Rats with infarction developed marked cardiomegaly, indicating the presence of chronic left ventricular dysfunction. The ratio of the norepinephrine metabolite, 3,4-dihydroxyphenylethylene glycol (DHPG) to norepinephrine (NE) was elevated in the right ventricle of rats with infarction, suggesting a chronic increase in cardiac sympathetic activity. Perindopril therapy commenced either immediately following infarction or 4 weeks following infarction reduced DHPG/NE ratios toward normal levels, and prevented or reversed cardiac hypertrophy. In contrast, chlorothiazide therapy significantly reduced DHPG/NE ratios but did not decrease cardiac hypertrophy. Perindopril reverses or prevents cardiac hypertrophy and chronic cardiac sympathetic hyperactivity following myocardial infarction, while chlorothiazide reduces cardiac sympathetic activity without influencing cardiomegaly.
Howes
L G
LG
University of Melbourne, Department of Medicine, Heidelberg, Victoria, Australia.
Hodsman
G P
GP
Rowe
P R
PR
Johnston
C I
CI
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy* / Q000209:etiology; D002740:Chlorothiazide / Q000627:therapeutic use*; D005260:Female; D007211:Indoles / Q000627:therapeutic use*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009203:Myocardial Infarction / Q000150:complications*; D009638:Norepinephrine / Q000378:metabolism; D020913:Perindopril; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D008734:Methoxyhydroxyphenylglycol; D002740:Chlorothiazide; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine; D020913:Perindopril