Proteinase activity in isolated glomeruli of Goldblatt hypertensive rats

In Goldblatt rats, the kidney exposed to high blood pressure reveals glomerulosclerosis. Moreover, in preexisting parenchymal renal disease, the development of glomerulosclerosis is accelerated in the unclipped kidney. Up to now, the pathogenetic mechanism underlying the development of glomerulosclerosis due to systemic hypertension has not completely been resolved. Traditionally, hemodynamic mechanisms have been discussed. This study was performed to investigate whether there might be a decreased activity of glomerular proteinases in the unclipped kidney of Goldblatt rats as a potential pathogenetic factor for glomerulosclerosis. 20 weeks after the surgical intervention, we found a reduced proteinase activity in ultrasonically destroyed isolated glomeruli obtained by differential sieving technique in comparison with the contralateral clipped kidney and the kidneys of sham-operated normotensive controls. This could be confirmed, when proteinase activity was related to DNA instead of protein. When investigating glomerular cathepsin B-content, a lysosomal enzyme, which is able to degrade glomerular structural as well as non-structural proteins, we found a decreased level in the kidney of Goldblatt rats exposed to systemic hypertension in comparison with normotensive control animals. Basing on these results we presume that glomerular protein accumulation and concomitant glomerulosclerosis due to systemic hypertension might be a result of a synergistical interaction between hemodynamic factors and biochemical ones; we suggest one of the latter to be a decreased glomerular proteinase activity.