Brown Norway chromosome 13 confers protection from high salt to consomic Dahl S rat

Consomic rats (SS.BN13), in which chromosome 13 from normotensive inbred Br own Norway rats from a colony maintained at the Medical College of Wisconsi n (BN/Mcw) was introgressed into the background of Dahl salt-sensitive (SS/ Mcw) rats, also maintained in a colony at the Medical College of Wisconsin, were bred. The present studies determined the mean arterial pressure (MAP) responses to salt and renal and peripheral vascular responses to norepinep hrine and angiotensin II; 24-hour protein excretion and histological analys es were used to assess renal pathology in rats that received a high salt (4 % NaCl) diet for 4 weeks. MAP of rats measured daily during the fourth week averaged 170+/-3.3 mm Hg in SS/Mcw rats, 119+/-2.1 mm Hg in SS.BN13 rats, and 103+/-1.3 mm Hg in BN/Mcw rats. After salt depletion, MAP fell an avera ge of 27+/-4.5 mm Hg in SS/Mcw rats, 9+/-2.6 mm Hg in SS.BN13 rats, and 11/-3.0 mm Hg in BN/Mcw rats. Protein excretion of SS/Mcw rats on a high salt diet averaged 189+/-30 mg/24 h, 63 +/- 18 mg/24 h in SS.BN13 rats, and 40/-6.4 mg/24 h in BN/Mcw rats. Compared with SS.BN13 and BN/Mcw rats, SS/Mcw rats exhibited significantly greater increases of renal vascular resistanc e in response to intravenous norepinephrine and angiotensin II. Severe medu llary interstitial fibrosis and tubular necrosis after a high salt diet wer e found consistently in SS/Mcw rat kidneys but were largely absent in the S S.BN13 and BN/Mcw rat kidneys. A similar degree of glomerular sclerosis was found in both SS/Mcw and SS.BN13 rats. In rats fed a 0.4% salt diet, the g lomerular filtration rate of SS/Mcw rats was significantly less than that o f BN/Mcw and SS.BN13 rats. These results reveal a powerful gene, or set of genes, within chromosome 13 of BN/Mcw rats that confers protection from the detrimental effects of high salt to the SS/Mcw rats.