Kikkawa K, Murata S, Iwasaki H, Toriumi W, Banno K, Nagao T
Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Arzneimittelforschung. 1992 Jun;42(6):781-6.
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.
在盐负荷易中风自发性高血压大鼠（SHRSP）中，研究了用克仑硫卓（(+)(2S,3S)-3-乙酰氧基-8-氯-5-[2-(二甲氨基)乙基]-2,3-二氢-2-(4-甲氧基苯基)-1,5-苯并硫氮杂卓-4(5H)-酮马来酸盐，TA-3090）进行长期治疗对血压、中风发生率、中风相关死亡率以及脑和其他器官组织学变化的影响。喂食含8%氯化钠饮食的雄性SHRSP在盐负荷3周后开始死于中风，同时伴有体重和食物摄入量下降。大多数大鼠（18只中的16只）在盐负荷第8周时死亡。用克仑硫卓（300或1000 ppm）进行长期治疗以剂量相关方式延迟了中风和死亡的发生，通过尾袖法测量时无任何降压作用。然而，在盐负荷3周后自由活动条件下用植入套管检查动脉血压的昼夜变化发现，1000 ppm克仑硫卓在黑暗期产生显著低血压，但在光照期未产生。组织学研究（盐负荷3周后）表明，1000 ppm克仑硫卓显著抑制了所研究的所有器官中的脑和肾损伤以及血管肥大。因此，克仑硫卓可预防盐负荷SHRSP中的中风，并保护肾损伤和血管肥大。克仑硫卓的降压作用和器官保护作用可能与其对中风的预防作用有关。
