KRH-594, a new angiotensin AT1 receptor antagonist, prevents end-organ damage in stroke-prone spontaneously hypertensive/Izm rats. 2001

Y Inada, and S Tazawa, and M Murakami, and M Akahane
Pharmacology Laboratory, Kissei Pharmaceutical Co. Ltd, Hotaka, Nagano, Japan. yoichi_inada@pharm.kissei.co.jp

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.

UI MeSH Term Description Entries
D006973 Hypertension Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more. Blood Pressure, High,Blood Pressures, High,High Blood Pressure,High Blood Pressures
D007676 Kidney Failure, Chronic The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION. ESRD,End-Stage Renal Disease,Renal Disease, End-Stage,Renal Failure, Chronic,Renal Failure, End-Stage,Chronic Kidney Failure,End-Stage Kidney Disease,Chronic Renal Failure,Disease, End-Stage Kidney,Disease, End-Stage Renal,End Stage Kidney Disease,End Stage Renal Disease,End-Stage Renal Failure,Kidney Disease, End-Stage,Renal Disease, End Stage,Renal Failure, End Stage
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D009929 Organ Size The measurement of an organ in volume, mass, or heaviness. Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D011918 Rats, Inbred SHR A strain of Rattus norvegicus with elevated blood pressure used as a model for studying hypertension and stroke. Rats, Spontaneously Hypertensive,Rats, SHR,Inbred SHR Rat,Inbred SHR Rats,Rat, Inbred SHR,Rat, SHR,Rat, Spontaneously Hypertensive,SHR Rat,SHR Rat, Inbred,SHR Rats,SHR Rats, Inbred,Spontaneously Hypertensive Rat,Spontaneously Hypertensive Rats
D011921 Rats, Inbred WKY A strain of Rattus norvegicus used as a normotensive control for the spontaneous hypertensive rats (SHR). Rats, Wistar Kyoto,Wistar Kyoto Rat,Rats, WKY,Inbred WKY Rat,Inbred WKY Rats,Kyoto Rat, Wistar,Rat, Inbred WKY,Rat, WKY,Rat, Wistar Kyoto,WKY Rat,WKY Rat, Inbred,WKY Rats,WKY Rats, Inbred,Wistar Kyoto Rats
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013777 Tetrazoles

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