PROTECTIVE EFFECTS OF ME3221 ON HYPERTENSIVE COMPLICATIONS AND LIFE-SPAN IN SALT-LOADED STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

1. A comparison was made on the protective effects of the following: M E3221, a competitive angiotensin AT(1) receptor antagonist; losartan, in which a major active metabolite is a non-competitive angiotensin AT (1) receptor antagonist; and enalapril, an angiotensin-converting enzy me inhibitor, using the salt-loaded stroke-prone spontaneously hyperte nsive rats (SHRSP). 2. SHRSP received orally ME3221 (3 and 10 mg/kg pe r day), losartan (10 mg/kg per day) and enalapril (10 mg/kg per day) f rom the 6th to the 20th week of age. All the control rats showed rapid elevation of systolic blood pressure (SEP), accompanied by hypertensi ve complications, and died by 15 weeks of age. 3. ME3221, losartan and enalapril suppressed the elevation of SEP in the salt-loaded SHRSP to a comparable degree, ME3221 and losartan increased the survival rate to >90%, and diminished hypertensive complications such as cerebral ap oplexy (stroke), renal injury (increased proteinuria, and total N-acet yl-beta-D-glucosaminidase activity) and heart failure (cardiac hypertr ophy and pleural effusion). 4. Competitive (ME3221) and non-competitiv e (losartan) angiotensin AT(1) receptor antagonists showed comparable efficacy against the complications and mortality of the salt-loaded SH RSP; both were more potent than enalapril in the protective effect.