Substitution of chromosome 1 ameliorates L-NAME hypertension and renal disease in the fawn-hooded hypertensive rat

Linkage analysis studies previously identified genetic loci associated with proteinuria and hypertension on chromosome 1 of fawn-hooded hypertensive (FHH) rats. The present studies were performed on conscious male and female rats to evaluate the influence of transfer of chromosome 1 from the Brown Norway (BN) rat to the FHH genetic background (FHH-1^BN). Rats were maintained for 2 wk on 8.0% NaCl chow with N^G-nitro-L-arginine methyl ester (L-NAME) in the drinking water (12.5 mg/l) to induce hypertension and accelerate the onset of renal disease. Mean arterial blood pressure (MAP) was significantly higher in the male FHH (188 ± 3 mmHg, n = 13) compared with the BN (121 ± 3 mmHg, n = 8); MAP in the FHH-1^BN was midway between the two parental strains (167 ± 5 mmHg, n = 9). Urinary protein and albumin excretion rates in the male FHH-1^BN (Uprot = 189 ± 36 mg/day, Ualb = 69 ± 16 mg/day, n = 10) were also midway between levels observed in the FHH (Uprot = 485 ± 54 mg/day; Ualb = 206 ± 25 mg/day, n = 13) and the BN (Uprot = 32 ± 5 mg/day, Ualb = 5 ± 1 mg/day, n = 8). Creatinine clearance was elevated, and the degree of glomerular damage was significantly reduced in the FHH-1^BN compared with the FHH. Qualitatively similar results were obtained from female FHH, FHH-1 ^BN, and BN rats. The present results indicate that genes contributing to L-NAME-induced hypertension and renal disease are found on chromosome 1 of the FHH rat.