GENETIC PREDISPOSITION TO HYPERTENSION AND MICROVASCULAR INJURY IN THE REMNANT KIDNEY MODEL

Genetic factors have been implicated in the development and progressio n of glomerulosclerosis and nephron loss in both experimental animals and in humans. The influence of a differing genetic predisposition to hypertension was examined in the remnant kidney (RK) model of progress ive glomerulosclerosis. Dahl salt-sensitive (S) and salt-resistant (R) rats fed a normal salt diet underwent either sham surgery or approxim ately 5/6 renal ablation and were studied 2 to 3 weeks later. Renal ab lation resulted in significantly more severe hypertension in RK-S rats (205 +/- 6.3 mm Hg, mean +/- SEM) compared with RK-R rats (153 +/- 3. 5 mm Hg; p <0.01). Renal autoregulatory ability, a protective mechanis m against renal transmission of systemic hypertension, was normal in b oth S and R rats with intact renal mass. Renal ablation resulted in si milar impairments of renal autoregulatory ability in both strains. How ever, striking differences in the severity of renal microvascular and glomerular injury were observed between the remnant kidneys of S and R rats, paralleling the differences in the severity of hypertension. Th e RK-S rats exhibited acute fibrinoid necrosis and thrombosis of glome rular capillaries, arterioles, and small arteries, whereas only mild s egmental glomerulosclerosis lesions were observed in a small percentag e of glomeruli in the RK-R rats. The intact kidneys of both strains we re essentially free of glomerular or vascular lesions. These data sugg est that a genetic predisposition to hypertension is a major determina nt of the severity of hypertension that follows severe reduction of re nal mass and the severity of the resulting hypertension, in tum, criti cally influences the severity of glomerular injury in the RK model.