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 devel opment of hypertensive cerebral lesions, we used immunohistochemical m ethods to study the distribution and level of nitric oxide synthase (N OS) in the brain of stroke-prone spontaneously hypertensive rats (SHRS Ps). The early changes in the brain of SHRSPs were petechiae, edema an d massive glial accumulation around fibrin deposits, which contained n ecrotized microvessels, whereas advanced cerebral lesions comprised ma ssive bleeding, cavity formation and diffuse degeneration of the white matter. In the normotensive control rats, immunoreactivity for NOS wa s demonstrated in scattered neuronal cells, as has been reported previ ously, but there was no reactivity in glial cells. In the present stud y in SHRSPs, however, considerable NOS immunoreactivity was observed i n most reactive astrocytes and in a proportion of the microglial cells and macrophages in the vicinity of the cortical lesions and in the su bcortical white matter both ipsi- and contralateral to the cortical le sion, The nerve cells in the edematous region also showed weak immunor eactivity for NOS. The distribution of increased NOS in SHRSP brains c orresponded well with the sites of extravasated plasma fluid as demons trated by anti-fibrinogen antibody. Based on these findings, we postul ate that edema and the simultaneously generated free radicals or some extravasated plasma components may induce expression of NOS in the rea ctive cells and nerve cells, and that the NO thus generated may be inv olved in the development of hypertensive cerebral lesions.