Glial endothelin/nitric oxide system participates in hippocampus CA1 neuronal death of SHRSP following transient...

1. When delayed neuronal death occurred in the hippocampus CA1 pyramidal cell layer of stroke-prone spontaneously hypertensive rats (SHRSP) at 4 and 7 days after a 10 min bilateral carotid occlusion and reperfusion, intense endothelin-1 (ET-1)- and ET-3-like immunoreactivities became evident in astrocytes in the damaged hippocampus CA1 subfields. 2. We also observed that microglia equipped with an ETB receptor aggregated within the CA1 pyramidal cell layer with neuronal death. 3. There was a dramatic increase in nitric oxide synthase (NOS) activity in astrocytes and microglia in the damaged hippocampus CA1 subfields. 4. Thus, the possibility that microglia with the ETB receptor are activated to produce NO, a neurotoxic factor, by astrocytic ET-1 and ET-3 produced in response to transient forebrain ischaemia would have to be considered.