Effect of angiotensin-converting enzyme inhibition on myocardial fibrosis and function in hypertrophied and failing myocardium from the spontaneously hypertensive rat.
BACKGROUND
After a period of stable hypertrophy, male spontaneously hypertensive rats (SHR) develop heart failure between 18 to 24 months of age, with depression of active myocardial function and increased passive stiffness. We tested the hypothesis that chronic ACE inhibition by captopril would prevent and possibly reverse impairment of myocardial function.


RESULTS
Male SHR and normotensive Wistar-Kyoto rats (WKY) were assigned to no treatment or captopril treatment (2 g/L in drinking water) begun at ages 12, 18, and 21 months; animals were studied at 24 months of age, or earlier when evidence of heart failure was found in SHR (mean age, 19+/-2 months). In an additional group, captopril treatment was begun when SHR developed heart failure; surviving animals were studied at 24 months of age. In untreated SHR, relative to WKY, isometric stress development at Lmax, maximum rate of stress development, and shortening velocity were depressed, whereas passive stiffness was increased, in association with the development of myocardial fibrosis. In the SHR treated before cardiac dysfunction, captopril administration attenuated hypertrophy and prevented contractile dysfunction, fibrosis, and increased passive stiffness. Captopril treatment begun after cardiac function was impaired reduced left ventricular hypertrophy but did not restore intrinsic contractile function or reduce fibrosis or passive stiffness.


CONCLUSIONS
In the male SHR, early treatment with captopril was associated with the most marked attenuation of dysfunction relative to the untreated SHR. Treatment initiated after the onset of heart failure improved clinical signs of heart failure and decreased left ventricular hypertrophy in surviving animals but did not reverse the fibrosis and contractile dysfunction associated with heart failure.
Brooks
W W
WW
Department of Veterans Affairs Medical Center, Boston, Mass 02130, USA. conrad.chester@boston.va.gov
Bing
O H
OH
Robinson
K G
KG
Slawsky
M T
MT
Chaletsky
D M
DM
Conrad
C H
CH
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D002216:Captopril / Q000494:pharmacology*; D002303:Cardiac Output, Low / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D004452:Echocardiography; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril