Krh-594, A New Angiotensin At1 Receptor Antagonist, Ameliorates Nephropathy And Hyperlipidaemia In Diabetic Spontaneously Hypertensive Rats

SUMMARY 1. We examined whether KRH‐594, a new angiotensin AT1 receptor antagonist, ameliorates the progression of diabetic nephropathy and hyperlipidaemia in streptozotocin (STZ)‐induced diabetic unilateral nephrectomized spontaneously hypertensive rats (DM‐1K‐SHR) or not. 2. The oral administration of KRH‐594 (3 and 10 mg/kg per day) and candesartan cilexetil (1 mg/kg per day) for 16 weeks significantly reduced systolic blood pressure, urinary albumin and urinary total protein in DM‐1K‐SHR. 3. In a histological study, KRH‐594 (3 and 10 mg/kg per day) and candesartan cilexetil (0.3 and 1 mg/kg per day) dose‐dependently improved glomerulosclerosis and the hyalin cast of tubules in DM‐1K‐SHR kidneys. Both KRH‐594 (10 mg/kg per day) and candesartan cilexetil (0.3 and 1 mg/kg per day) dose‐dependently inhibited cardiac hypertrophy. 4. KRH‐594 (3 and 10 mg/kg per day), but not candesartan cilexetil, dose‐dependently reduced the levels of triglyceride, total cholesterol and phospholipids in DM‐1K‐SHR. 5. These results suggest that KRH‐594 improves diabetic complications, such as nephropathy and hyperlipidaemia, with hypertension.