The possible role of lysosomal enzymes in the pathogenesis of hypertensive cerebral lesions in spontaneously hypertensive rats.

In an attempt to clarify the role of lysosomal enzymes in the developmental mechanisms of cerebral lesions under chronic hypertensive conditions, we biochemically investigated the activities of acid phosphatase (AcPase), N-acetyl beta-glucosaminidase (NAGase) and cathepsin B (CathB) in the cerebral cortex and subcortical white matter in stroke-prone spontaneously hypertensive rats (SHRSPs). We also investigated enzyme-histochemically the activities of AcPase and NAGase, and immunohistochemically the distribution of CathB. The activities of all enzymes tended to increase with advancing age. The enzyme activities in the aged SHRSPs were in general higher than those in normotensive rats, the differences being significant at 24 weeks of age. Histochemical investigation showed that SHRSPs had an increased number of cells with positive reaction to these enzymes in the edematous cortex with and without vascular changes, and degenerated subcortical white matter. These cells with positive reaction were made up of reactively increased astrocytes and microglia. Neurons in the edematous area also showed slightly intensified enzyme activities. The present studies suggest that chronic hypertension or chronic edema due to hypertension causes increased activities of lysosomal enzymes in the cerebral cortex and subcortical white matter and, thus, that activated lysosomal enzymes may take part in the developmental mechanisms of cystic formation as well as the diffuse degeneration of the white matter.