Transfer of Brown Norway Rat Chromosome 13 into Dahl S Genomic Background Confers Protection from High Salt Diet

Abstract

P132 Consomic rats (SS BN13 ) were bred in which chromosome 13 from normotensive inbred Brown Norway (BN/Mcw) rats was introgressed into the background of Dahl salt-sensitive (SS/Mcw) rats. The present studies determined the mean arterial pressure (MAP) responses to salt; renal and peripheral vascular responses to norepinephrine (NE) and angiotensin II (AngII); and protein excretion and renal histology in rats that received a high salt (4% NaCl) for 3 weeks. Indwelling arterial catheters were implanted in the 2 nd week of high salt and MAP was recorded for 3 days during the 3 rd week of high salt, and again 36 hours after 10mg/kg Lasix and return to a low salt (0.4%) diet. Results: High salt MAP of SS/Mcw rats averaged 183+4 mmHg, SS BN13 averaged 124+3 mmHg, and BN/Mcw averaged 132+4 mmHg. The reduction in MAP with sodium depletion averaged 31.8+3 mmHg in SS/Mcw rats but was significantly less in SS BN13 rats (14.7+1.6 mmHg) and BN/Mcw rats (13.9+2 mmHg). Protein excretion of SS/Mcw rats on high salt averaged 270+31 mg/24hr compared to 55+22 mg/24hr in SS BN13 rats, and 19+7 mg/24hr in BN/Mcw rats. Reduction of renal blood flow to iv administration of NE and AngII, was significantly greater SS/Mcw rats compared to SS BN13 and BN/Mcw rats. Severe medullary interstitial fibrosis and tubular necrosis was consistently seen in SS/Mcw rat kidneys but not in the SS BN13 or BN/Mcw rats following 3 weeks of high salt intake. These results demonstrate the power of functional mapping of complex traits using chromosomal transfer techniques and reveal a powerful gene (or set of genes) within BN/Mcw chromosome 13 that confers protection from the detrimental effects of a high salt diet to the Dahl salt-sensitive rat (SS/Mcw). It remains to be determined if the renoprotective effect is secondary to the reduction in blood pressure with chromosomal transfer, or a direct protective effect.