Normotensive fawn-hooded (FHL) rats are susceptible to develop renal damage after L-name-induced hypertension

We have developed two inbred strains of fawn-hooded (FH) rats that differ in their rate of progression of renal damage. Compared to the hypertensive FHH rat, the age-matched normotensive FHL rat has a lower level of proteinuria (UpV) and less focal glomerulosclerosis (FGS), resulting in a longer survival time. Genetic studies using a backcross of the FHH and ACI strains, revealed a region on rat chromosome 1 (named Rf-1) that was linked with UpV but not with hypertension, indicating that these traits were under separate genetic control. Rf-1 may be an important determinant of hypertension-associated renal damage. Comparison of FHH and FHL rat genotypes indicated that the Rf-1 region was similar in both strains. This made us surmise that a blood pressure increase in the FHL rat should produce more severe UpV and FGS than in the ACI strain. This was tested by treating 6 weeks old rats chronically with L-NAME in a dose of either 100 or 250 mg/l drinking fluid. Tail cuff systolic blood pressure (SBP), UpV, and the incidence of FGS were assessed after 7 or 11 weeks of treatment. In both strains L-NAME caused a dose dependent increase in SBP. At similar levels of SBP, the increase in UpV was significantly higher in FHL compared to ACI. Survival was also affected by L-NAME treatment. With the highest dose, all FHL rats died before the end of the 11 week follow-up, while all 6 ACI rats did survive. The incidence of FGS was also significantly higher in FHL rats. Our findings clearly indicate that compared to ACI rats, FHL rats are more susceptible to develop renal damage after induction of hypertension by chronic L-NAME treatment. This fits with our previous observations that in rats the susceptibility to develop hypertension-associated renal damage is genetically determined.