KRH-594, a new angiotensin AT1 receptor antagonist, prevents end-organ damage in stroke-prone spontaneously hypertensive/Izm rats.
1. In the present study, we examined whether KRH-594, a new angiotensin AT1 receptor antagonist, would stop the progression of renal failure and end-organ damage and improve the survival rate in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP/Izm). 2. Oral administration of KRH-594 (3 and 10 mg/kg per day) for 11 weeks significantly reduced systolic blood pressure, urinary total protein, blood urea nitrogen, serum creatinine and urinary N-acetyl glucosaminidase and increased creatinine clearance in SHRSP/Izm. 3. In a histological study, KRH-594 (3 and 10 mg/kg per day) significantly improved the glomerulosclerosis, basophilic change and hyalin cast of tubules, proliferation of afferent arterioles and interlobular artery wall scores of the kidney and the cardiac fibrosis scores of the heart in SHRSP/Izm. KRH-594 (3 and 10 mg/kg per day) also significantly inhibited cardiac hypertrophy. 4. KRH-594 (3 and 10 mg/kg per day) prevented death in SHRSP/Izm during the examination period. 5. These results suggest that KRH-594 improves hypertensive complications, such as renal failure, cardiac hypertrophy and thickening of the artery wall, and prevents death in salt-loaded SHRSP/Izm.
Inada
Y
Y
Pharmacology Laboratory, Kissei Pharmaceutical Co. Ltd, Hotaka, Nagano, Japan. yoichi_inada@pharm.kissei.co.jp
Tazawa
S
S
Murakami
M
M
Akahane
M
M
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D018450:Disease Progression; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D007676:Kidney Failure, Chronic / Q000473:pathology / Q000517:prevention & control; D008099:Liver / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D020521:Stroke / Q000235:genetics / Q000473:pathology*; D015996:Survival Rate; D013777:Tetrazoles / Q000627:therapeutic use*; D013830:Thiadiazoles / Q000627:therapeutic use*
D057911:Angiotensin Receptor Antagonists; C108799:KRH 594; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D013830:Thiadiazoles