Altered nitric oxide synthase immunoreactivity in the brain of stroke-prone spontaneously hypertensive rats.

To obtain information about the role of nitric oxide (NO) in the development of hypertensive cerebral lesions, we used immunohistochemical methods to study the distribution and level of nitric oxide synthase (NOS) in the brain of stroke-prone spontaneously hypertensive rats (SHRSPs). The early changes in the brain of SHRSPs were petechiae, edema and massive glial accumulation around fibrin deposits, which contained necrotized microvessels, whereas advanced cerebral lesions comprised massive bleeding, cavity formation and diffuse degeneration of the white matter. In the normotensive control rats, immunoreactivity for NOS was demonstrated in scattered neuronal cells, as has been reported previously, but there was no reactivity in glial cells. In the present study in SHRSPs, however, considerable NOS immunoreactivity was observed in most reactive astrocytes and in a proportion of the microglial cells and macrophages in the vicinity of the cortical lesions and in the subcortical white matter both ipsi- and contralateral to the cortical lesion. The nerve cells in the edematous region also showed weak immunoreactivity for NOS. The distribution of increased NOS in SHRSP brains corresponded well with the sites of extravasated plasma fluid as demonstrated by anti-fibrinogen antibody. Based on these findings, we postulate that edema and the simultaneously generated free radicals or some extravasated plasma components may induce expression of NOS in the reactive cells and nerve cells, and that the NO thus generated may be involved in the development of hypertensive cerebral lesions.