PROTECTIVE EFFECTS OF CANDESARTAN CILEXETIL (TCV-116) AGAINST STROKE,KIDNEY DYSFUNCTION AND CARDIAC-HYPERTROPHY IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

The effects of chronic treatment with an angiotensin II receptor antag onist, candesartan cilexetil (TCV-116, 0.1, 1, 10 mg/kg), and an angio tensin converting enzyme inhibitor, enalapril maleate (enalapril, 10 m g/kg), on the development of end-organ damage were examined in stroke- prone spontaneously hypertensive rats (SHRSP). The control SHRSP devel oped severe hypertension with stroke signs and increased urinary prote in excretion, TCV-116 (0.1 mg/kg) reduced the stroke incidence and uri nary protein excretion without affecting the blood pressure. TCV-116 ( 1 and 10 mg/kg) and enalapril reduced blood pressure, the stroke incid ence, the urinary indices and left ventricular weight. Circulating ren in-angiotensin system (RAS) and renal renin mRNA expression were signi ficantly accelerated or tended to be accelerated in the control SHRSP with end-organ damages. A low dose of TCV-116 tended to reduce the RAS indices in plasma by improving the damages, whereas a high dose (10 m g/kg) increased them by the reflexes with blocking RAS. The present re sults indicate that chronic All blockade reduces the increase in blood pressure, end-organ damages and RAS related to the damages in SHRSP.