Role of Endothelin in Sodium Balance

描述：(申请人提供)：这项建议的目的是 内皮素B受体在调节肾压中的作用 排钠和血压调节。1988年，柳泽明和同事们 鉴定了一种后来称为内皮素的内皮衍生多肽 (EL)。内皮素受体的两个主要亚型已被鉴定，ETA 和ETB受体。这两种受体都位于肾脏中，与 最高浓度的ETB受体出现在延髓内。虽然 Eta受体在病理生理学中的作用已经得到了很好的描述。 关于高血压，ETB受体在调节中的生理重要性 肾压性钠尿和血压调节尚不清楚。 我们实验室的初步数据表明，EL的肾脏产生 因慢性钠负荷而增强。此外，我们实验室的数据表明 慢性ETB受体阻断会导致钠敏感的 高血压。高血压的确切调节机制 然而，由慢性ETB受体阻断所致，目前尚不清楚。具体目标 要解决的问题是：1)测试ET系统是 因钠摄入量增加而上调2)以检验这一假设 慢性ETB受体阻断所致高血压与 血压-尿钠关系中的慢性高血压转变3) 对确定肾髓质的假设进行检验起着重要作用 在介导慢性ETB受体阻断所致高血压中的作用 检验一氧化氮合成减少中介还原的假设 ETB受体对肾功能和动脉压升高的影响 封锁性高血压。

DESCRIPTION: (provided by applicant): The objective of this proposal is to examine the role of endothelin B receptors in modulating renal-pressure natriuresis and blood pressure regulation. In 1988, Yanagsawa and co-workers characterized an endothelial-derived peptide subsequently called endothelin (El). Two major subtypes of endothelin receptors have been characterized, ETA and ETB receptors. Both of these receptors are located in the kidney with the highest concentration of ETB receptors occurring within the medulla. Although the role of ETA receptors have been well characterized in the pathophysiology of hypertension, the physiological importance of ETB receptors in modulating renal-pressure natriuresis and blood pressure regulation is unclear. Preliminary data from our laboratory indicates that the renal production of El is enhanced by chronic Na loading. Moreover, data from our laboratory indicates that chronic ETB receptor blockade results in a Na-sensitive form of hypertension. The exact mechanisms involved in mediating the hypertension induced by chronic ETB receptor blockade, however, are unknown. Specific aims to be addressed are: 1) To test the hypothesis that the ET system is upregualted in response to increases in Na intake 2) To test the hypothesis that the hypertension induced by chronic ETB receptor blockade is associated with a chronic hypertensive shift in the pressure-natriuresis relationship 3) to test the hypothesis that determine the renal medulla plays an important role in mediating the hypertension induced by chronic ETB receptor blockade 4) To test the hypothesis that reduced nitric oxide synthesis mediates the reduction in renal function and elevation in arterial pressure during ETB receptor blockade-induced hypertension.