The influence of chronic treatment with
clentiazem ((+)(2S,3S)-3-acetoxy-8-chloro-5-[2-(dimethylamino)ethyl]-2,3-dihydro- 2-(4-methoxyphenyl)-1,5-benzothiazepin-4 (5H)-one
maleate,
TA-3090), on blood pressure, incidence of
stroke,
stroke-related mortality and histological changes of the brain and other organs were examined in
salt-loaded
stroke-prone spontaneously hypertensive rats (SHRSP). Male SHRSP that were fed an 8% NaCl-containing diet began to die of a
stroke 3 weeks after
salt-loading, accompanied by decreases in
body weight and food intake. Most of the rats (16 out of 18) died by the 8th week of
salt-loading. Chronic treatment with
clentiazem (300 or 1000 ppm) delayed the occurrence of
stroke and death in a dose-related manner without any hypotensive action when measured by the tail-cuff method. However, examination of circadian changes in arterial blood pressure with implanted
cannula under a freely-moving condition 3 weeks after
salt-loading revealed that 1000 ppm
clentiazem produced significant
hypotension in the dark phase but not in the light phase. Histological studies (3 weeks after
salt-loading) showed that 1000 ppm
Clentiazem significantly suppressed the cerebral and renal damages, and vascular
hypertrophy in all organs studied. Thus,
clentiazem prevents
stroke and also protects renal damage and vascular
hypertrophy in
salt-loaded SHRSP. The hypotensive effect and organ-protective action by
clentiazem may be involved in its prophylactic action against
stroke.