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EFFECT OF CHRONIC TREATMENT WITH ME3221 ON BLOOD PRESSURE AND MORTALITY IN AGED STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Author(s) -
Nagura Jun,
Hui Chen,
Yamamoto Mikio,
Yasuda Sumie,
Abe Mitsuhiro,
Hachisu Mitsugu,
Konno Fukio
Publication year - 1995
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1995.tb02955.x
Subject(s) - medicine , enalapril , losartan , blood pressure , stroke (engine) , proteinuria , heart failure , cardiology , endocrinology , angiotensin converting enzyme , angiotensin ii , kidney , mechanical engineering , engineering
Summary 1. The protective effect of ME3221, a surmountable AT 1 antagonist, on the hypertension and its concomitant complications in aged (32 week old) stroke‐prone spontaneously hypertensive rats (SHRSP) was studied following long‐term (32 weeks) oral administration, and compared with those of losartan (metabolite EXP3174 is an insurmountable AT 1 antagonist) and enalapril. 2. During the treatment period, ME3221, at a dose of 10 mg/kg per day steadily reduced the systolic blood pressure, and no tolerance was developed to the fall in blood pressure. The reference drugs showed similar activity, but the anti‐hypertensive effect of ME3221 was more potent. 3. In the control group, rats began to die from 52 weeks of age and all rats had died by 64 weeks of age. In contrast, no rats treated with ME3221, losartan or enalapril died before 64 weeks of age. 4. ME3221, losartan and enalapril suppressed the hypertensive complications observed in control SHRSP, that is, cerebral apoplexy (stroke and cerebral oedema), renal injury (increased proteinuria, total N‐acetyl‐β‐d‐glucosaminidase activity and ascites) and heart failure (cardiac hypertrophy and pleural effusion). 5. These results indicate that ME3221 has a stable anti‐hypertensive effect, prevents hypertensive complications and prolongs survival in aged SHRSP equally as well as losartan and enalapril.