ME3221, A SURMOUNTABLE ANGIOTENSIN AT(1)-RECEPTOR ANTAGONIST, PREVENTS HYPERTENSIVE COMPLICATIONS IN AGED STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

The protective effects of ME3221, thoxy-2,6-dimethyl-4-[[2'-(1H-tetraz ol-5-yl)-1,1'- biphenyl-4-yl]methoxy] pyridine, on aged (32-week-old) stroke-prone spontaneously hypertensive rats (SHRSP) were studied foll owing long-term (for 8 months) oral administration. At a dose of 10 mg /kg/day, ME3221 suppressed the mortality and the hypertensive complica tions observed in control SHRSP: cerebral apoplexy (hemorrhage, and sp ongeform and malacia in the cerebral cortex), increased proteinuria, a nd total N-acetyl-beta-D-glucosaminidase activity, and cardiac hypertr ophy and pleural effusion. The protective activity of ME3221, a surmou ntable angiotensin AT(1)-receptor antagonist, was comparable to losart an, an insurmountable AT(1)-antagonist, and also to enalapril, an angi otensin-converting enzyme inhibitor. In addition, ME3221 reduced the s ystolic blood pressure more effectively than the two reference drugs.