Angiotensin converting enzyme inhibitors attenuate ischemic brain metabolism in hypertensive rats.
OBJECTIVE
Angiotensin converting enzyme (ACE) inhibitors are expected to modulate neuronal activities. The present study was designed to examine the beneficial effects of ACE inhibitors on microcirculation and metabolism in the ischemic brain.


METHODS
Cerebral ischemia was developed for 60 minutes in spontaneously hypertensive rats (SHR, n = 35) by bilateral carotid artery occlusion. ACE inhibitor (0.1 or 10 mg/kg SQ 29,852 or captopril) were intravenously injected 15 minutes before cerebral ischemia. Cerebral blood flow to the parietal cortex was measured with the H2 clearance technique. Lactate, pyruvate, and ATP in the brain were estimated by the enzymatic method.


RESULTS
Before cerebral ischemia, high doses of both SQ 29,852 and captopril significantly decreased mean arterial pressure by 15 to 25 mm Hg and reduced cerebral vascular resistance by 13% to 17% of the resting values. Cerebral blood flow and arterial pressure during ischemia were not altered by these ACE inhibitors. After 60 minutes of cerebral ischemia, tissue lactate in vehicle-treated SHR increased 6.6-fold and ATP decreased to 65% of the control values. Administration of SQ 29,852 or captopril significantly reduced the lactate levels to 1.6- to 3.1-fold and well preserved the ATP levels to 82% to 93% of the control.


CONCLUSIONS
These results suggest that inhibition of ACE activities may be protective for cerebral metabolism against ischemic insult.
Sadoshima
S
S
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Fujii
K
K
Ooboshi
H
H
Ibayashi
S
S
Fujishima
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D005260:Female; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000503:physiopathology; D007773:Lactates / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010296:Parietal Lobe / Q000098:blood supply; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D007773:Lactates; D009943:Organophosphorus Compounds; D011773:Pyruvates; D000255:Adenosine Triphosphate; D011392:Proline; D002216:Captopril; C054518:ceronapril