Diverse effects of AT(1) receptor antagonists on normal blood pressure andregulatory system

An AT(1) receptor antagonist, losartan, has been reported to improve surviv al and quality of life in patients with congestive heart failure as angiote nsin converting enzyme inhibitors do. Since many of the patients are normot ensive, it may be a drawback if the compound decreases normal blood pressur e. In this study, we investigated whether a novel AT(1) receptor antagonist , TA-606, which is more potent than losartan, affects normal blood pressure and its regulatory system in comparison with losartan. TA-606 (30 and 100 mg/kg, p.o.) did not change normal blood pressure, whereas losartan (100 mg /kg, p.o.) tended to decrease it. Although EXP3174 (1 and 10 mg/kg, i.v.), an active metabolite of losartan, suppressed the baroreceptor-heart rate (H R) reflex, 606A (1 and 10 mg/kg, i.v.), an active metabolite of TA-606, did not affect it. Since losartan is known to affect the L-glutamate receptor which is part of the central blood pressure regulatory system, we also inve stigated whether 606A affects L-glutamate receptor binding. We found that 6 06A did not affect the binding of the L-glutamate receptor, but EXP3174 inh ibited the binding with IC50 values of 13.3 mu M. These findings suggest th at, even having the same AT(1) receptor antagonist properties as losartan a nd EXP3174, TA-606 and its active metabolite do not influence normal blood pressure or its regulatory system.