ABNORMAL PRESSURE NATRIURESIS IN HYPERTENSION

肾灌注压与排钠的关系 在调节体液容量和动脉中起重要作用 压力 在原发性高血压的动物模型中， 血压-尿钠排泄关系似乎以这种方式改变 “高血压”肾脏在给定的时间内排泄较少的钠和水， 肾灌注压水平。 本提案的目的是 是检查肾间质静水压力在这一过程中的作用， 改变压力-尿钠排泄关系，并确定肾单位 负责增强钠重吸收的位点。 全肾 将使用清除和微穿刺技术评估功能 两种原发性高血压动物模型的肾功能紊乱。 的 使用的模型是自发性高血压大鼠（SHR）和Dahl 盐敏感性高血压大鼠（Dahl S）。 以获得进一步 了解肾灌注压与 钠排泄，这项建议还将审查直接影响 肾间质静水压力增加对钠排泄的影响， 利用一种技术（由PI开发）， 间质流体静压通过注射异山梨醇盐水到 通过长期植入聚乙烯基质胶囊治疗肾结石。 需要解决的具体问题是： 1)在SHR和Dahl S中改变的压力-尿钠排泄关系 大鼠由于肾血管阻力高， 间质流体静压？ 2)肾间质流体静力学的直接增加 SHR和Dahl S大鼠钠排泄压力减弱？ 3)哪一个肾单位部位参与了 SHR和Dahl S大鼠 4)哪个肾单位部位受到肾间质直接增加的影响 静水压？ 深肾单位对肾脏的变化是否更敏感 间质流体静压比浅表肾单位高？ 对这些问题的回答应提供与 理解改变关系的基本机制 动物肾灌注压与尿钠排泄的关系 与人类原发性高血压非常相似的高血压模型。

The relationship between renal perfusion pressure and sodium excretion plays an important role in regulating body fluid volumes and arterial pressure. In animal models of essential hypertension, the pressure-natriuresis relationship appears to be altered in such a manner that the "hypertensive" kidney excretes less sodium and water for a given level of renal perfusion pressure. The objective of the present proposal is to examine the role of renal interstitial hydrostatic pressure in this altered pressure-natriuresis relationship and to determine the nephron sites responsible for the enhanced sodium reabsorption. Whole kidney clearance and micropuncture techniques will be used to assess functional renal derangements in two animal models of essential hypertension. The models to be used are the spontaneously hypertensive rat (SHR) and the Dahl salt sensitive hypertensive rat (Dahl S). To obtain a further understanding of the relationship between renal perfusion pressure and sodium excretion, this proposal will also examine the effects of direct increases in renal interstitial hydrostatic pressure on sodium excretion, utilizing a technique (developed by PI) which directly increases renal interstitial hydrostatic pressure by injecting isoncotic saline into the renal interstitium via chronically implanted polyethylene matrix capsules. Specific questions to be addressed are: 1) Is the altered pressure-natriuresis relationship in the SHR and Dahl S rats due to high renal vascular resistance associated with reduced renal interstitial hydrostatic pressure? 2) Are the effects of direct increases in renal interstitial hydrostatic pressure on sodium excretion blunted in the SHR and Dahl S rats? 3) Which nephron site is involved in the enhanced sodium reabsorption in the SHR and Dahl S rats? 4) Which nephron site is affected by direct increases in renal interstitial hydrostatic pressure? Are deep nephrons more sensitive to changes in renal interstitial hydrostatic pressure than superficial nephrons? Answers to these questions should provide new information relevant to the understanding of the basic mechanism involved in the altered relationship between renal perfusion pressure and urinary sodium excretion in animal models of hypertension closely resembling human essential hypertension.