Angiotensin II receptor blockers (ARBs) are known to prevent ischemic brain damage after
stroke.
Natriuretic peptides, which are increased by a
neprilysin inhibitor, are also reported to protect against brain damage. Therefore, we investigated the possible protective effect of
valsartan (VAL) compared with
LCZ696 (VAL+
neprilysin inhibitor; 1:1) after middle cerebral artery (MCA) occlusion. Eight-week-old male C57BL/6J mice were treated with VAL (3mg/kg per day) or
LCZ696 (6mg/kg per day) for 2 weeks before MCA occlusion. Blood pressure and heart rate were measured by telemetry. Cerebral blood flow (CBF) was determined by
laser-Doppler flowmetry. Ischemic area was evaluated by triphenytetrasodium
chloride staining, and oxidative stress was determined by
dihydroethidium staining. Blood pressure and heart rate were not significantly different before and
after treatment. Pre-treatment with
LCZ696 or VAL reduced the ischemic area, and this effect of
LCZ696 was more marked than that of VAL pre-treatment. The decrease in CBF in the peripheral region of the ischemic area was significantly attenuated by pre-treatment with
LCZ696 or VAL, without any significant effect on CBF in the core region. VAL or
LCZ696 pre-treatment significantly decreased the increase of
superoxide anion production in the cortex on the ischemic side. However, no significant difference in CBF and
superoxide anion production was observed between VAL and
LCZ696 pre-treatment. The preventive effect of
LCZ696 on ischemic brain damage after
stroke was more marked than that of VAL.
LCZ696 could be used as a new approach to prevent brain damage after
stroke. (246 words).