ME-3221 is an angiotensin AT1 receptor antagonist that prevents hypertensive complications in aged stroke-prone hypertensive rats.

ME3221 inhibited the pressor response to angiotensin II in rats at doses of 0.3-1.0 mg/kg. Higher doses of ME3221 (3-10 mg/kg) were required to achieve the same inhibitory potency in dogs.The antagonistic potency of ME3221 against angiotensin II-induced contraction in rabbit aorta (pA2 = 8.82) was approximately fivefold higher than in canine aorta (pA2 = 8.18).[1];Long-term (8 months) oral administration of ME3221 (10 mg/kg/d) to aged (32 weeks) stroke-prone hypertensive rats (SHRSP) suppressed mortality and hypertensive complications observed in control SHRSP: stroke (hemorrhage, spongiosis and flaccidity in the cerebral cortex), increased proteinuria, total N-acetyl-β-D-glucosaminidase activity and cardiac hypertrophy and pleural effusion. [2]；SHRSP were orally administered ME3221 (3 and 10 mg/kg per day) from 6 to 20 weeks, and ME3221 inhibited to a considerable extent the elevation of SBP in salt-containing SHRSP, increased survival to >90%, and reduced hypertensive complications such as stroke (moderate), renal injury (increased proteinuria and total N-acetyl-β-D-glucosaminidase activity), and heart failure (cardiac hypertrophy and pleural effusion). [3]