Antihypertensive effects of the treatment with ATZ and losartan in L-NAME hypertensive rats

Previous works suggest that hydrogen peroxide (H2O2), a reactive oxygen species, attenuates brain angiotensin II-mediated hypertension in rats. Moreover, the subcutaneous (s.c.) administration of 3-amino-1,2,4-triazole (ATZ), a catalase inhibitor that increases H2O2 availability, reduces hypertension and sympathetic activity simultaneously with an increase in angiotensinergic activity in spontaneously hypertensive rats (SHRs). It is not clear how much the increase in angiotensinergic activity affects the sympatho-inhibition and the antihypertensive effect of ATZ, and if this is specific for SHRs. The present study evaluated the effects of s.c. ATZ and losartan (angiotensin II AT1 antagonist), alone or combined for 7 days, on mean arterial pressure (MAP) in nitric oxide synthase-inhibited hypertensive rats (L-NAME model). In addition, angiotensinergic and sympathetic activities were also investigated using acute intravenous losartan and hexamethonium (ganglionic blocker) in the same rats. The treatment with ATZ + losartan s.c. reduced MAP slightly below to normotensive levels in L-NAME hypertensive rats (88 ± 8, vs. L-NAME + saline: 162 ± 7 mmHg), whereas s.c. losartan alone partially reduced MAP (133 ± 7 mmHg). The hypotensive responses produced by hexamethonium were reduced in rats treated with ATZ + losartan s.c. (-44 ± 12, vs. L-NAME + saline: -71 ± 6 mmHg), suggesting that the treatment with ATZ + losartan s.c. significantly reduced sympathetic activation in L-NAME-treated rats. These findings suggest that the combination of ATZ and losartan efficiently blocks sympathetic and angiotensinergic activation in L-NAME hypertensive rats, abolishing hypertension. Further research is necessary on the mechanisms of H2O2 and ATZ antihypertensive action.