Role of Endothelin in Sodium Balance

描述：（由申请人提供）：本提案的目的是 检测内皮素B受体在调节肾压中的作用 尿钠排泄和血压调节。1988年，柳泽和同事们 其特征在于一种内皮衍生肽， （El）.内皮素受体的两种主要亚型已被表征，ETA ETB受体。这两种受体都位于肾脏中， 最高浓度的ETB受体出现在髓质内。虽然 ETA受体在病理生理学中的作用已得到充分表征 ETB受体在调节高血压中的生理重要性， 肾压尿钠排泄和血压调节尚不清楚。 我们实验室的初步数据表明，肾脏产生的El 慢性钠负荷增强。此外，我们实验室的数据表明， 慢性ETB受体阻断导致Na-敏感形式的 高血压介导高血压的确切机制 然而，由慢性ETB受体阻断剂诱导的抗肿瘤作用尚不清楚。具体目标 要解决的问题是：1）为了检验假设，ET系统是 随着钠摄入量的增加而升高2）为了检验假设 慢性ETB受体阻断引起的高血压与 压力-尿钠排泄关系中的慢性高血压转变3） 为了验证这一假设，决定肾髓质在 在介导慢性ETB受体阻滞剂诱导的高血压中的作用4）To 测试假设，减少一氧化氮合成介导减少 肾功能和动脉压升高 阻塞性高血压

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.