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Thromb Haemost 2000; 83(05): 722-727
DOI: 10.1055/s-0037-1613899
Review Article
Schattauer GmbH

Protective Effects of Imidapril on He-Ne Laser-Induced Thrombosis in Cerebral Blood Vessels of Stroke-Prone Spontaneously Hypertensive Rats

Yasuto Sasaki
1   From the Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University, Kobe, Japan
,
Takanori Noguchi   *
1   From the Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University, Kobe, Japan
,
Junji Seki
2   Department of Biomedical Engineering, National Cardiovascular Center Research Institute, Suita, Japan
,
J. C. Giddings
3   Department of Haematology, University of Wales College of Medicine, Cardiff, UK
,
Junichiro Yamamoto
1   From the Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University, Kobe, Japan
› Author AffiliationsWe thank to Tanabe Pharmaceutical Co. LTD. for providing imidapril and imidaprilat and we also appreciate to Grants-in-Aid for Scientific Research (No. 09670678) from the Ministry of Education and Sports and Health Science Research of Kobe Gakuin University.
Further Information

Publication History

Received 22 March 1999

Accepted after resubmission 11 January 2000

Publication Date:
08 December 2017 (online)

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Summary

Inhibitors of angiotensin converting enzyme (ACE) have been developed recently for therapeutic purposes in hypertension and ischemic cardiovascular diseases. Ogiku et al. (1) reported that one such inhibitor, imidapril, significantly prolonged survival in stroke-prone spontaneously hypertensive rats (SHRSP). The present study was designed to investigate the effect of imidapril on cerebral blood vessels in SHRSP to clarify role of the ACE inhibitor in mechanisms of cerebral thrombosis and stroke. Imidapril was administered orally at 1.0 and 5.0 mg/kg/day for 3 weeks from the age of 7 weeks, and was shown to prevent the usual increase in blood pressure seen in these animals. It also delayed He-Ne laser-induced cerebral thrombosis and increased significantly the plasma concentration of nitric oxide metabolites (NO2/NO3). To confirm the association between nitric oxide (NO) and these effects of imidapril, an inhibitor of nitric oxide synthase, NG - nitro-L-arginine methyl ester hydrochloride (L-NAME) was dissolved in drinking water and administered to the animals for 3 weeks. Four of six rats died from stroke when L-NAME was given alone. When imidapril (5.0 mg/kg/day) was administered with L-NAME, however, the animals showed no signs or symptoms of stroke. In these instances, therefore, the concurrent administration of L-NAME with imidapril reversed significantly the effects of imidapril. Intravenous injection of imidaprilat (100 µg/kg), an active metabolite of imidapril, also decreased blood pressure significantly and increased the plasma levels of NO2/NO3 after 5 min. Moreover, imidaprilat enlarged arteriolar diameters and caused an increase in red cell velocity and mean blood flow in pial arterioles after 15 min.

The results strongly suggested that imidapril protects cerebral vessels in SHRSP by elevating the release of NO, thereby improving the cerebral circulation and reducing the tendency to thrombosis and stroke.

Keywords

ACE-inhibitor - imidapril - thrombosis - nitric oxide - pial vessel

* Present address: Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan


 

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