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PROTECTIVE EFFECTS OF ME3221 ON HYPERTENSIVE COMPLICATIONS AND LIFESPAN IN SALT‐LOADED STROKE‐PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Author(s) -
Nagura Jun,
Yamamoto Mikio,
Hui Chen,
Yasuda Sumie,
Hachisu Mitsugu,
Konno Fukio
Publication year - 1996
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.1440-1681.1996.tb02601.x
Subject(s) - losartan , enalapril , medicine , angiotensin ii receptor type 1 , endocrinology , blood pressure , angiotensin ii , stroke (engine) , angiotensin ii receptor antagonist , proteinuria , angiotensin receptor , antagonist , angiotensin converting enzyme , receptor , kidney , mechanical engineering , engineering
SUMMARY 1. A comparison was made on the protective effects of the following: ME3221, a competitive angiotensin AT 1 receptor antagonist; losartan, in which a major active metabolite is a non‐competitive angiotensin AT 1 receptor antagonist; and enalapril, an angiotensin‐converting enzyme inhibitor, using the salt‐loaded stroke‐prone spontaneously hypertensive rats (SHRSP). 2. SHRSP received orally ME3221 (3 and 10mg/kg per day), losartan (10mg/kg per day) and enalapril (10mg/kg per day) from the 6th to the 20th week of age. All the control rats showed rapid elevation of systolic blood pressure (SBP), accompanied by hypertensive complications, and died by 15 weeks of age. 3. ME3221, losartan and enalapril suppressed the elevation of SBP in the salt‐loaded SHRSP to a comparable degree. ME3221 and losartan increased the survival rate to >90%, and diminished hypertensive complications such as cerebral apoplexy (stroke), renal injury (increased proteinuria, and total N ‐acetyl‐β‐D‐glucosaminidase activity) and heart failure (cardiac hypertrophy and pleural effusion). 4. Competitive (ME3221) and non‐competitive (losartan) angiotensin AT 1 receptor antagonists showed comparable efficacy against the complications and mortality of the salt‐loaded SHRSP; both were more potent than enalapril in the protective effect.