ME3221, a surmountable angiotensin AT1-receptor antagonist, prevents hypertensive complications in aged stroke-prone spontaneously hypertensive rats.

Abstract

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.

• Authors: J Nagura, C Hui, M Yamamoto, S Yasuda, M Abe, M Hachisu, F Konno
• Journal: Japanese journal of pharmacology (Jpn J Pharmacol) Vol. 71 Issue 1 Pg. 39-49 (May 1996) ISSN: 0021-5198 [Print] Japan
• PMID: 8791170 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Angiotensin Receptor Antagonists
• Antihypertensive Agents
• Biphenyl Compounds
• Imidazoles
• ME 3221
• Tetrazoles
• Enalapril
• Losartan

Topics

• Angiotensin Receptor Antagonists
• Animals
• Antihypertensive Agents (therapeutic use)
• Biphenyl Compounds (therapeutic use)
• Blood Pressure (drug effects)
• Brain (drug effects)
• Cerebrovascular Disorders (etiology, prevention & control)
• Enalapril (therapeutic use)
• Heart (drug effects)
• Hypertension (complications, drug therapy)
• Imidazoles (therapeutic use)
• Kidney (drug effects, pathology)
• Losartan
• Male
• Myocardium (pathology)
• Rats
• Rats, Inbred SHR
• Tetrazoles (therapeutic use)