This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ogiku, N. Articles by Ishida, R. Search for Related Content PubMed PubMed Citation Articles by Ogiku, N. Articles by Ishida, R.

Stroke, Vol 24, 245-252, Copyright © 1993 by American Heart Association

ARTICLES

Prophylactic effect of imidapril on stroke in stroke-prone spontaneously hypertensive rats

N Ogiku, H Sumikawa, Y Hashimoto and R Ishida
Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.

BACKGROUND AND PURPOSE: 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.

This article has been cited by other articles:

				T. Nakamura, E. Yamamoto, K. Kataoka, T. Yamashita, Y. Tokutomi, Y.-F. Dong, S. Matsuba, H. Ogawa, and S. Kim-Mitsuyama Pioglitazone Exerts Protective Effects Against Stroke in Stroke-Prone Spontaneously Hypertensive Rats, Independently of Blood Pressure Stroke, November 1, 2007; 38(11): 3016 - 3022. [Abstract] [Full Text] [PDF]

				S. Kim-Mitsuyama, E. Yamamoto, T. Tanaka, Y. Zhan, Y. Izumi, Y. Izumiya, T. Ioroi, H. Wanibuchi, and H. Iwao Critical Role of Angiotensin II in Excess Salt-Induced Brain Oxidative Stress of Stroke-Prone Spontaneously Hypertensive Rats Stroke, May 1, 2005; 36(5): 1077 - 1082. [Abstract] [Full Text] [PDF]

				A. K. Trauernicht, H. Sun, K. P. Patel, and W. G. Mayhan Enalapril Prevents Impaired Nitric Oxide Synthase-Dependent Dilatation of Cerebral Arterioles in Diabetic Rats Stroke, November 1, 2003; 34(11): 2698 - 2703. [Abstract] [Full Text] [PDF]

				S. Kawashima, T. Yamashita, Y. Miwa, M. Ozaki, M. Namiki, T. Hirase, N. Inoue, K.-i. Hirata, and M. Yokoyama HMG-CoA Reductase Inhibitor Has Protective Effects Against Stroke Events in Stroke-Prone Spontaneously Hypertensive Rats Stroke, January 1, 2003; 34(1): 157 - 163. [Abstract] [Full Text] [PDF]

				C. T. Abrahamsen, F. C. Barone, W. G. Campbell Jr., A. H. Nelson, L. C. Contino, M. A. Pullen, E. T. Grygielko, R. M. Edwards, N. J. Laping, and D. P. Brooks The Angiotensin Type 1 Receptor Antagonist, Eprosartan, Attenuates the Progression of Renal Disease in Spontaneously Hypertensive Stroke-Prone Rats with Accelerated Hypertension J. Pharmacol. Exp. Ther., April 1, 2002; 301(1): 21 - 28. [Abstract] [Full Text] [PDF]

				X.-L. Ma, F. Gao, A. H. Nelson, B. L. Lopez, T. A. Christopher, T.-L. Yue, and F. C. Barone Oxidative Inactivation of Nitric Oxide and Endothelial Dysfunction in Stroke-Prone Spontaneous Hypertensive Rats J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 879 - 885. [Abstract] [Full Text]

				F. C. Barone, R. W. Coatney, S. Chandra, S. K. Sarkar, A. H. Nelson, L. C. Contino, D. P. Brooks, W. G. Campbell Jr., E. H. Ohlstein, and R. N. Willette Eprosartan reduces cardiac hypertrophy, protects heart and kidney, and prevents early mortality in severely hypertensive stroke-prone rats Cardiovasc Res, June 1, 2001; 50(3): 525 - 537. [Abstract] [Full Text] [PDF]

				R. Rocha, P. N. Chander, K. Khanna, A. Zuckerman, and C. T. Stier Jr. Mineralocorticoid Blockade Reduces Vascular Injury in Stroke-Prone Hypertensive Rats Hypertension, January 1, 1998; 31(1): 451 - 458. [Abstract] [Full Text] [PDF]