ME3221, a Surmountable Angiotensin AT_1-Receptor Antagonist, Prevents Hypertensive Complications in Aged Stroke-Prone Spontaneously Hypertensive Rats

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The protective effects of ME3221, 3-met hoxy-2, 6-dimethyl-4-[[2-(1H-tetrazol-5-yl)-1, 1-biphenyl-4-yl]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-β-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.
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