KRH-594, a new angiotensin AT1 receptor antagonist, ameliorates nephropathy and hyperlipidaemia in diabetic spontaneously hypertensive rats.
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 10mg/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.
Inada
Y
Y
Pharmacological Laboratories, Kissei Pharmaceutical Co Ltd, Minamiazumi, Nagano, Japan. yoichi_inada@pharm.kissei.co.jp
Murakami
M
M
Tazawa
S
S
Akahane
M
M
D000419:Albuminuria / Q000652:urine; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology / Q000517:prevention & control*; D003928:Diabetic Nephropathies / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D006321:Heart / Q000187:drug effects; D006949:Hyperlipidemias / Q000097:blood / Q000517:prevention & control*; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008055:Lipids / Q000097:blood; D009206:Myocardium / Q000473:pathology; D009392:Nephrectomy; D009929:Organ Size / Q000187:drug effects; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles / Q000494:pharmacology*; D013830:Thiadiazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001786:Blood Glucose; C108799:KRH 594; D008055:Lipids; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D013830:Thiadiazoles