Open AccessME3221, a Surmountable Angiotensin AT1-Receptor Antagonist, Prevents Hypertensive Complications in Aged Stroke-Prone Spontaneously Hypertensive Rats
Author(s) -
Jun Nagura,
Hui Chen,
Mikio Yamamoto,
Sumie Yasuda,
Mitsuhiro Abe,
Mitsugu Hachisu,
Fukio Konno
Publication year - 1996
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.71.39
Subject(s) - medicine , losartan , enalapril , angiotensin ii receptor type 1 , antagonist , blood pressure , endocrinology , stroke (engine) , angiotensin converting enzyme , angiotensin ii receptor antagonist , angiotensin ii , proteinuria , receptor antagonist , receptor , kidney , mechanical engineering , engineering
The protective effects of ME3221, 3-methoxy-2,6-dimethyl-4-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4-y l]methoxy] pyridine, on aged (32-week-old) stroke-prone spontaneously hypertensive rats (SHRSP) were studied following long-term (for 8 months) oral administration. At a dose of 10 mg/kg/day, ME3221 suppressed the mortality and the hypertensive complications observed in control SHRSP: cerebral apoplexy (hemorrhage, and spongeform and malacia in the cerebral cortex), increased proteinuria, and total N-acetyl-beta-D-glucosaminidase activity, and cardiac hypertrophy and pleural effusion. The protective activity of ME3221, a surmountable angiotensin AT1-receptor antagonist, was comparable to losartan, an insurmountable AT1-antagonist, and also to enalapril, an angiotensin-converting enzyme inhibitor. In addition, ME3221 reduced the systolic blood pressure more effectively than the two reference drugs.