The brain is a possible target for an angiotensin-converting enzyme inhibitor in the treatment of chronic heart failure.
BACKGROUND
Although many lines of evidence have shown beneficial effects of angiotensin-converting enzyme (ACE) inhibitors on patients with chronic heart failure (CHF) after myocardial infarction (MI), the target of ACE inhibitors still remains unclear. The objectives of the present study were to evaluate the dipsogenic response to centrally administered angiotensin and to examine the effect of central administration of an ACE inhibitor on cardiac remodeling in rats with CHF after large MI.


RESULTS
The drinking responses to intracerebroventricular (i.c.v.) injections of saline and angiotensin I (100 ng) were measured in 22 male Sprague-Dawley rats with or without CHF at 2-5 weeks after the ligation of the left coronary artery. The dipsogenic responses to i.c.v. angiotensin I were significantly larger in rats with CHF and large MI (infarct size > 30%) than in sham-operated rats. Pretreatment with losartan abolished the significant difference between the two groups. Left ventricular (LV) weights of 32 surviving rats with CHF were measured after the 3-week subcutaneous infusions of vehicle (s.c.-VEH) and captopril (1 mg x kg(-1) x h(-1), s.c.-CAP) or the 3-week i.c.v. infusions of vehicle (i.c.v.-VEH) and captopril (50 microg x kg(-1) x h(-1), i.c.v.-CAP). The LV weights normalized by body weights of s.c.-CAP rats were significantly smaller than those of s.c.-VEH rats (1.73 +/- 0.04 vs 2.08 +/- 0.09 g x kg(-1); P < .01); those of i.c.v.-CAP rats were also significantly smaller than those of i.c.v.-VEH rats (1.84 +/- 0.08 vs 2.1 +/- 0.10 g x kg(-1); P < .05).


CONCLUSIONS
These results suggest that the brain is a possible target for ACE inhibitors in the treatment of CHF after MI.
Sato
T
T
Department of Cardiovascular Dynamics, National Cardiovascular Center Research Institute, Suita, Osaka, Japan.
Yoshimura
R
R
Kawada
T
T
Shishido
T
T
Miyano
H
H
Sugimachi
M
M
Sunagawa
K
K
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology* / Q000627:therapeutic use*; D005069:Evaluation Studies as Topic; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology; D006439:Hemodynamics; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002216:Captopril; D019808:Losartan