Ionic Homeostasis in Hypovolemia: Renal Mechanisms

低血容量时的离子稳态：肾脏机制

• 批准号: 6551471
• 负责人: Randi Beth Silver
• 金额: $ 39.88万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6551471
• 关键词: angiotensins; bicarbonates; electrolyte balance; hydrogen potassium exchanging ATPase; hypovolemia; laboratory rat; membrane transport proteins; potassium ion; renal tubular transport

DESCRIPTION (provided by applicant): Keeping serum K+ within narrowly defined limits is critical for the maintenance of life. K+ homeostasis is an essential need of the body, but the means by which K^+ is conserved are poorly understood. K+-sparing is an important homeostatic component in response to volume depletion as may occur in such conditions as diarrhea, diuretic use, and congestive heart failure. The kidney adapts to volume depletion by reabsorbing more NaCI but the means by which K+ is conserved when NaCI is reabsorbed is not understood. The overall objective of this project is to elucidate the renal K+ conserving mechanisms involved in the adaptation to hypovolemia. I propose that K reabsorption occurs in volume depletion via a mechanism involving H+-K+-ATPase proteins present in the intercalated cells of the cortical collecting duct and these proteins are responsible for preserving K+-balance under conditions of volume depletion. Further, I propose that the apical Cl-/HCO-3 exchanger in the base secreting intercalated cell subtype, in cortical collecting duct, is the mechanism by which Cl-reabsorption accompanies Na+ reabsorption. Specific Aim I will examine the effect of volume depletion in in vitro studies on the activities of the H+-K+ ATPase and CI/HCO-3 exchanger in intercalated cells of cortical collecting tubules, and H+-K+-ATPase abundance and localization in renal cortex homogenate and in fixed kidney from control and volume depleted rats. In vivo studies will be performed on the effects of angiotensin, part of the renin-angiotensin-aldosterone system, which is stimulated in voluime depletion, on H+-K+-ATPase activity and Cl/HCO-3 exchange rate. Specific Aim II will investigate the role of angiotensin in acutely regulating the function of H+-K+-ATPases and the Cl-/HCO-3 exchanger in intercalated cells in vitro. Two signal transduction pathways associated with the actions of angiotensin will be studied in order to determine how angiotensin exerts its effects on intercalated cell transport. The overall premise for conducting these experiments is that if we understand the physiological basis by which the body normaIly conserves K+, then we will also have identified a target that potentially can be exploited for therapy of disorders of K+ metabolism.

描述（由申请人提供）：将血清K+保持在狭义定义的范围内对于维持生命至关重要。 K+稳态是身体的必要需求，但是对K^+的保守手段知之甚少。 k+sparing是响应体积耗竭的重要稳态成分，因为在腹泻，利尿剂使用和充血性心力衰竭等条件下可能发生。 肾脏可通过重吸收更多NACI来适应体积耗竭，但是当Naci被重新吸收时，K+保存的手段尚不清楚。 该项目的总体目的是阐明适应低血容量的肾脏K+保存机制。 我提出，K重吸收在体积耗竭中通过涉及皮质收集导管插入细胞中H+-K+-ATPase蛋白的机制发生，并且这些蛋白质负责在体积耗竭条件下保留K+平衡。 此外，我建议在皮质收集导管中，基部分泌互插细胞亚型的顶端Cl-/hco-3交换器是Cl抗吸收伴随Na+重新吸收的机制。 具体目的，我将研究体外耗竭在体外研究中对H+-K+ATPase和CI/HCO-3交换器在皮质收集小管的插入细胞中的活性，H+-K+-K+-K+-K+-ATPase丰度和肾脏肾脏中的肾脏均具有同质性肾脏和肾脏中的肾脏中的肾脏和体积depleted and Emplepleted depleted depleted depleted depleted depleted。 体内研究将对血管紧张素的作用进行，血管紧张素是肾素 - 血管紧张素 - 醛固酮系统的一部分，该系统在挥发性耗竭，H+-K+-ATPase活性和Cl/HCO-3汇率上受到刺激。 具体的目标II将研究血管紧张素在体外中插入细胞中H+-K+-ATPases和Cl-/HCO-3交换器急性调节的作用。 将研究与血管紧张素作用相关的两种信号转导途径，以确定血管紧张素如何对其对插层细胞转运产生影响。 进行这些实验的总体前提是，如果我们了解身体正常地保存K+的生理基础，那么我们还将确定一个可能利用的靶标，可以利用它来治疗K+代谢的疾病。