RENAL MECHANISMS OF K DEPLETION IN METABOLIC ACIDOSIS

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。

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.