Salt-Sensitive Hypertension, Renal Injury, and Renal Vasodysfunction Associated With Dahl Salt-Sensitive Rats Are Abolished in Consomic SS.BN1 Rats.
Salt-Sensitive Hypertension, Renal Injury, and Renal Vasodysfunction Associated With Dahl Salt-Sensitive Rats Are Abolished in Consomic SS.BN1 Rats.
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DOI：
10.1161/jaha.120.020261
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发表时间：
2021-11-02
影响因子：
5.4
通讯作者：
Polichnowski AJ
中科院分区：
文献类型：
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作者：
Potter JC;Whiles SA;Miles CB;Whiles JB;Mitchell MA;Biederman BE;Dawoud FM;Breuel KF;Williamson GA;Picken MM;Polichnowski AJ
对盐负荷的异常肾血流动力学反应被认为是导致盐敏感性（SS）高血压的原因。然而，这主要是基于麻醉动物的研究，在有意识的SS和耐盐大鼠中几乎没有数据。我们评估了清醒、长期使用仪器的10至14周龄Dahl SS和consomic SS大鼠在给予0.4% NaCl和高盐（4.0% NaCl）饮食期间的动脉血压、肾功能和肾血流量，其中耐盐Brown-Norway品系的1号染色体渗入SS品系（SS. BN 1）的基因组。三周的高盐摄入显著增加了SS大鼠的血压（20%），并加重了肾损伤。相比之下，Brown‐Norway和SS. BN 1大鼠的血压升高（5%）同样减弱，两种品系均完全免受肾损伤。在SS. BN 1大鼠中，高盐摄入1周与肾血管阻力显著降低（-8%）和肾血流量增加（15%）相关。相反，肾血管阻力未能降低，肾血流量保持不变，在SS大鼠在高盐摄入。最后，在0.4%NaCl和高盐摄入期间，SS和SS. BN 1大鼠的尿钠排泄和肾小球滤过率相似。我们的数据支持肾血管功能障碍导致Dahl SS大鼠血压盐敏感性的概念，并且大鼠1号染色体上的基因在调节盐负荷和盐诱导的高血压的肾血流动力学反应中起主要作用。
Abnormal renal hemodynamic responses to salt‐loading are thought to contribute to salt‐sensitive (SS) hypertension. However, this is based largely on studies in anesthetized animals, and little data are available in conscious SS and salt‐resistant rats. We assessed arterial blood pressure, renal function, and renal blood flow during administration of a 0.4% NaCl and a high‐salt (4.0% NaCl) diet in conscious, chronically instrumented 10‐ to 14‐week‐old Dahl SS and consomic SS rats in which chromosome 1 from the salt‐resistant Brown‐Norway strain was introgressed into the genome of the SS strain (SS.BN1). Three weeks of high salt intake significantly increased blood pressure (20%) and exacerbated renal injury in SS rats. In contrast, the increase in blood pressure (5%) was similarly attenuated in Brown‐Norway and SS.BN1 rats, and both strains were completely protected against renal injury. In SS.BN1 rats, 1 week of high salt intake was associated with a significant decrease in renal vascular resistance (−8%) and increase in renal blood flow (15%). In contrast, renal vascular resistance failed to decrease, and renal blood flow remained unchanged in SS rats during high salt intake. Finally, urinary sodium excretion and glomerular filtration rate were similar between SS and SS.BN1 rats during 0.4% NaCl and high salt intake. Our data support the concept that renal vasodysfunction contributes to blood pressure salt sensitivity in Dahl SS rats, and that genes on rat chromosome 1 play a major role in modulating renal hemodynamic responses to salt loading and salt‐induced hypertension.