ME3221, a surmountable angiotensin AT1-receptor antagonist, prevents hypertensive complications in aged stroke-prone spontaneously hypertensive rats.
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.
Nagura
J
J
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Yokohama, Japan.
Hui
C
C
Yamamoto
M
M
Yasuda
S
S
Abe
M
M
Hachisu
M
M
Konno
F
F
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000517:prevention & control; D004656:Enalapril / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007093:Imidazoles / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D019808:Losartan; D008297:Male; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D013777:Tetrazoles / Q000627:therapeutic use*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; C093897:ME 3221; D013777:Tetrazoles; D004656:Enalapril; D019808:Losartan