Genetic background and the susceptibility of the kidney to pressure‐induced injury

Using a computer controlled aortic occluder between the renal arteries to chronically maintain perfusion pressure of the left kidney at normal levels while the right kidney is exposed to hypertension, we have reported that 85% of the renal injury of the Dahl salt‐sensitive hypertensive (SS) rat was the consequence of pressure‐induced renal injury (Hypertension 19:1472,2008). Given the wide variations of renal injury found among human hypertensive populations, we hypothesized that differences in genetic backgrounds may predispose the kidney to pressure‐induced renal injury. To test this hypothesis, renal injury was determined using inbred SS rats and compared to two consomic strains (SS.2 BN and SS.10 BN ; BN chr 2 or10 introgressed into SS) with similar salt‐sensitivity to SS rats. Similar levels of hypertension were achieved in each of these strains by day 14 of an 8% salt diet, but a 4x difference in renal injury (% casts) was found comparing uncontrolled right kidneys of SS vs SS.10 BN (4.1±0.5%; n=4 vs 1.0%±0.1%), and a 20x difference in SS vs SS.2 BN (0.2±.04%; n=3). Comparing the left controlled to the right uncontrolled kidneys, SS had a 122% left‐right difference, SS.10 BN a 25% and SS.2 BN <1% difference. These results indicate that susceptibility to pressure‐induced renal injury can have a strong genetic component (HL‐29587; HL‐81091)