Nitric oxide (NO) production by
endothelial nitric oxide synthase (eNOS) plays a protective role in
cerebral ischemia by maintaining vascular permeability, whereas NO derived from neuronal and inducible NOS is neurotoxic and can participate in neuronal damage occurring in
ischemia.
Matrix metalloproteinases (
MMPs) are up-regulated by ischemic injury and degrade the basement membrane if brain vessels to promote cell death and tissue injury. We previously reported that
agmatine, synthesized from
L-arginine by
arginine decarboxylase (ADC) which is expressed in endothelial cells, has shown a direct increased eNOS expression and decreased
MMPs expression in bEnd3 cells. But, there are few reports about the regulation of eNOS by
agmatine in ischemic animal model. In the present study, we examined the expression of eNOS and
MMPs by
agmatine treatment after transient global
ischemia in vivo. Global
ischemia was induced with four vessel occlusion (4-VO) and
agmatine (100 mg/kg) was administered intraperitoneally at the onset of reperfusion. The animals were euthanized at 6 and 24 hours after global
ischemia and prepared for other analysis. Global
ischemia led severe neuronal damage in the rat hippocampus and cerebral cortex, but
agmatine treatment protected neurons from ischemic injury. Moreover, the level and expression of eNOS was increased by
agmatine treatment, whereas inducible NOS (iNOS) and MMP-9
protein expressions were decreased in the brain. These results suggest that
agmatine protects microvessels in the brain by activation eNOS as well as reduces extracellular matrix degradation during the early phase of ischemic insult.