Prophylactic effect of imidapril on stroke in stroke-prone spontaneously hypertensive rats.
OBJECTIVE
It has been reported that some angiotensin converting enzyme inhibitors can prevent stroke-prone spontaneously hypertensive rats from stroke at much higher doses than clinical doses used for hypertension therapy. This study was performed to investigate the prophylactic effectiveness of imidapril against stroke in comparison with enalapril.


METHODS
Salt-loaded stroke-prone spontaneously hypertensive rats were orally given imidapril (0.5, 1, 2, and 5 mg/kg per day), enalapril (2 and 5 mg/kg per day), or hydralazine (5 mg/kg per day). Stroke signs were scored, and blood pressure, protein concentration, and N-acetyl-beta-D-glucosaminidase activity in urine were measured. After 2 weeks of medication, angiotensin converting enzyme activities in the aorta were measured 24 hours after dosing.


RESULTS
In the control group, severe hypertension developed, and all rats died within 12 weeks because of stroke. Imidapril and enalapril dose-dependently decreased the stroke-related mortality, and both agents at 5 mg/kg per day showed excellent prophylaxis, although they did not inhibit hypertensive development. Imidapril at 0.5 mg/kg per day significantly prevented stroke to almost the same extent as enalapril at 2 mg/kg per day or hydralazine at 5 mg/kg per day. Imidapril dose-dependently suppressed the elevation of the two urinary indexes, which was followed by stroke. Imidapril inhibited enzyme activity in the aorta more strongly than did enalapril at the same dose.


CONCLUSIONS
Imidapril prevented the incidence of stroke in stroke-prone spontaneously hypertensive rats at a dose of 0.5 mg/kg per day or more by amelioration of kidney dysfunction. Reduction of blood pressure is not necessary, although enzyme inhibition in the vasculature may partly relate to the effect.
Ogiku
N
N
Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Sumikawa
H
H
Hashimoto
Y
Y
Ishida
R
R
D000118:Acetylglucosaminidase / Q000652:urine; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D002561:Cerebrovascular Disorders / Q000401:mortality / Q000517:prevention & control* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004656:Enalapril / Q000008:administration & dosage*; D007093:Imidazoles / Q000008:administration & dosage*; D048289:Imidazolidines; D015994:Incidence; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D004656:Enalapril; C065166:imidapril; D000118:Acetylglucosaminidase