KRH-594, a new angiotensin AT1 receptor antagonist, ameliorates nephropathy and hyperlipidaemia in diabetic spontaneously hypertensive rats.

Abstract

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.

• Authors: Y Inada, M Murakami, S Tazawa, M Akahane
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 27 Issue 4 Pg. 270-6 (Apr 2000) ISSN: 0305-1870 [Print] Australia
• PMID: 10779124 (Publication Type: Journal Article)

Chemical References

• Angiotensin Receptor Antagonists
• Blood Glucose
• KRH 594
• Lipids
• Receptor, Angiotensin, Type 1
• Receptor, Angiotensin, Type 2
• Tetrazoles
• Thiadiazoles

Topics

• Albuminuria (urine)
• Angiotensin Receptor Antagonists
• Animals
• Blood Glucose (drug effects)
• Blood Pressure (drug effects)
• Body Weight (drug effects)
• Diabetes Mellitus, Experimental (physiopathology, prevention & control)
• Diabetic Nephropathies (pathology, physiopathology, prevention & control)
• Heart (drug effects)
• Hyperlipidemias (blood, prevention & control)
• Hypertension (pathology, physiopathology, prevention & control)
• Kidney (drug effects, pathology, physiopathology)
• Lipids (blood)
• Myocardium (pathology)
• Nephrectomy
• Organ Size (drug effects)
• Proteinuria (urine)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Receptor, Angiotensin, Type 1
• Receptor, Angiotensin, Type 2
• Tetrazoles (pharmacology)
• Thiadiazoles (pharmacology)