RENAL MECHANISMS OF K DEPLETION IN METABOLIC ACIDOSIS

代谢性酸中毒中钾消耗的肾脏机制

• 批准号: 3447309
• 负责人: DANIEL B. ORNT
• 金额: $ 5.2万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-23 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3447309
• 关键词: acidosis; adrenalectomy; aldosterone; chronic disease /disorder; dexamethasone; dietary potassium; hormone regulation /control mechanism; kidney metabolism; metabolism disorder; metabolism disorder diagnosis; potassium deficiency; renal tubular transport; saluresis; sodium

The purpose of the proposed studies is to determine the role of aldosterone in the maintenance of potassium (K) depletion during chronic metabolic acidosis (CMA). Hypokalemia and K depletion are common findings both in clinical and experimental CMA. In K depletion induced by dietary K restriction, we have demonstrated a renal adaptation for K conservation using isolated perfused kidneys from rats. However, the adaptation for K conservation was not functioning when kidneys from rats with K depletion secondary to CMA were perfused at normal pH. This lack of K conservation in vitro could not be attributed to increased sodium excretion although an increase in sodium excretion and urine flow are likely the etiologies of the initial K loss which occurs in early CMA. Aldosterone levels are likely increased during CMA and this hormone is a potent stimulus of K secretion. In the present study, adrenalectomized (ADX) rats will be rendered acidotic while receiving dexamethasone and low or high doses of aldosterone replacement or no aldosterone replacement. The degree of K depletion and acidosis will be assessed in balance studies. Kidneys, from ADX rats replaced with aldosterone during CMA, will be perfused at normal pH. If an elevation in aldosterone mediates K loss during CMA, kidneys from acidosis rats on low aldosterone replacement should react normally to K depletion and conserve K. These studies will provide further understanding in renal handling of K and factors regulating K conservation.

这些研究的目的是确定醛固酮在 在慢性代谢过程中维持钾（K）耗竭 酸中毒（CMA）。 低钾血症和钾缺乏是常见的结果， 临床和实验CMA。 日粮钾诱导的缺钾 限制，我们已经证明了肾脏适应钾守恒 使用大鼠的离体灌注肾脏。 然而，K的适应性 当钾缺乏大鼠的肾脏 在正常pH值下灌注。这种K保守性的缺乏 体外试验不能归因于钠排泄增加， 钠排泄和尿流量增加可能是 在CMA早期发生的初始K损失。 醛固酮水平是 可能在CMA期间增加，这种激素是K 分泌物 在本研究中，肾上腺切除（ADX）大鼠将 在接受地塞米松和低或高剂量的 醛固酮替代或无醛固酮替代。 K的程度 将在平衡研究中评估消耗和酸中毒。 肾脏，从 ADX大鼠在CMA期间用醛固酮替代，将在正常灌注 博士 如果醛固酮升高介导CMA期间的钾丢失， 从酸中毒大鼠低醛固酮替代反应正常， 钾素耗竭和保钾。 这些研究将进一步提供 了解肾脏对钾的处理和钾保存的调节因素。