1-Aminocyclopropanecarboxylic acid (ACPC) has been shown to protect neurons against
glutamate-induced neurotoxicity by reducing
N-methyl-D-aspartate (
NMDA) receptor activation. Recent studies have demonstrated that several antagonists of
NMDA receptors have important cardiovascular effects. In this study, we examined whether the cardiovascular effects of ACPC involve the role of
heme oxygenase-1 (HO-1) and its
antioxidant effect in
stroke-prone spontaneously hypertensive rats (SHRSP). Male SHRSP were divided into two groups: a control group and an ACPC group administered ACPC at 50 mg/kg per day for 4 weeks by peritoneal injection. Systolic blood pressure (SBP) and mortality of
stroke were significantly lower in the ACPC group than in the control group. Urinary Na(+) and Cl(-) excretion and plasma
superoxide dismutase (SOD) activity were increased in the ACPC group. Western analysis detected
proteins that were immunoreactive to anti-
nitrotyrosine antibody and showed lower levels of expression in the cerebral cortex compared to that in the control group. Immunohistochemical analysis revealed that
8-hydroxy-2'-deoxyguanosine (8-OHdG) formation in the hippocampus and cerebral cortex was reduced in the ACPC group. Quantitative reverse-transcription-polymerase chain reaction (RT-PCR) showed that administration of ACPC also significantly decreased the expression of
neuronal nitric oxide synthase (nNOS)
mRNA in the hippocampus and endotherial
nitric oxide synthase (eNOS)
mRNA in the cerebral cortex, and drastically increased HO-1
mRNA in the cerebral cortex. Enhanced HO-1 staining on sections from the hippocampus and cerebral cortex was observed in the ACPC group. These data suggest that the normalization by ACPC of blood pressure elevation and mortality of
stroke involves induction of the expression of HO-1, which exerts
antioxidant and vascular relaxation effects, in SHRSP.