Brown Norway chromosome 13 confers protection from high salt to consomic Dahl S rat
Brown Norway chromosome 13 confers protection from high salt to consomic Dahl S rat
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DOI：
10.1161/01.hyp.37.2.456
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发表时间：
2001-02-01
期刊：
影响因子：
8.3
通讯作者：
Jacob, HJ
中科院分区：
文献类型：
--
作者：
Cowley, AW;Roman, RJ;Jacob, HJ
将来自威斯康辛医学院（BN/Mcw）的正常近交系褐挪威大鼠的13号染色体与同样来自威斯康辛医学院（BN/Mcw）的达尔盐敏感（SS/Mcw）大鼠的13号染色体融合，培育出经济大鼠（SS. bn13）。目前的研究确定了平均动脉压（MAP）对盐的反应以及肾脏和外周血管对去甲肾上腺素和血管紧张素II的反应；采用24小时蛋白排泄和组织学分析来评估高盐（4% NaCl）饮食4周大鼠的肾脏病理。第四周每日测MAP， SS/Mcw大鼠平均170+/-3.3 mm Hg， SS. bn13大鼠平均119+/-2.1 mm Hg， BN/Mcw大鼠平均103+/-1.3 mm Hg。减盐后，SS/Mcw大鼠MAP平均下降27+/-4.5 mm Hg， SS. bn13大鼠MAP平均下降9+/-2.6 mm Hg， BN/Mcw大鼠MAP平均下降11+/-3.0 mm Hg。高盐饮食下SS/Mcw大鼠蛋白质排泄量平均为189+/-30 mg/24 h， SS. bn13大鼠为63 +/- 18 mg/24 h， BN/Mcw大鼠为40+/-6.4 mg/24 h。与SS. bn13和BN/Mcw大鼠相比，SS/Mcw大鼠在静脉注射去甲肾上腺素和血管紧张素II后肾血管阻力明显增加。高盐饮食后，SS/Mcw大鼠肾脏出现了严重的髓质间质纤维化和肾小管坏死，但SS. bn13和BN/Mcw大鼠肾脏基本没有出现这种情况。SS/Mcw和SS. bn13大鼠的肾小球硬化程度相似。在0.4%盐饲粮中，SS/Mcw大鼠的肾小球滤过率显著低于BN/Mcw和SS. bn13大鼠。这些结果揭示了BN/Mcw大鼠13号染色体中一个强大的基因或一组基因，该基因可保护SS/Mcw大鼠免受高盐的有害影响。
Consomic rats (SS.BN13), in which chromosome 13 from normotensive inbred Brown Norway rats from a colony maintained at the Medical College of Wisconsin (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 norepinephrine and angiotensin II; 24-hour protein excretion and histological analyses 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 average 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 resistance in response to intravenous norepinephrine and angiotensin II. Severe medullary interstitial fibrosis and tubular necrosis after a high salt diet were found consistently in SS/Mcw rat kidneys but were largely absent in the SS.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 glomerular filtration rate of SS/Mcw rats was significantly less than that of 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.