MECHANISM OF RENAL ACID/BASE HOMEOSTASIS

肾脏对酸碱平衡有重要贡献：1) 过滤后的小苏打的重吸收和2)净排酸。近期 我们实验室的研究已经阐明了这两种病毒 不同的过程受到监管。关于角色的新概念 铵转运，最受监管的净酸成分 排泄，以及它在酸碱平衡中的作用已经出现。此外， 钾平衡对铵排泄的影响已被阐明。 来自我们对慢性高钾血症的研究。此外，我们还探索了 并在多种模型中描述了尿酸的缺陷 远端肾小管性酸中毒。这样做的长期目标是 建议进行的一系列研究旨在扩大我们对 肾小管性酸中毒酸化缺陷的病理生理学研究 细胞和分子水平的高钾血症。要实现这一目标 我们将在大鼠离体髓内侧应用微灌注技术。 集合管(IMCD)体外灌流及乳头状微穿刺术 体内调查慢性高血钾对输尿管的影响 阻断和长期服用钒酸盐对大鼠体内质子分泌的影响 通过碳酸氢盐和铵的运输来衡量IMCD。相对的 两种质子的特异性抑制剂，双比拉霉素和SCM 28080 泵、H+-ATPase和H+-K+ATPase将分别用于 确定这些泵在酸化缺陷中的作用。第二， 我们将确定皮质部和髓质部集合管和IMCD 培养的RCCT细胞表达H+-K+ATPase信使RNA，并 如果这个泵的表达受酸碱和钾的调节 动态平衡。

The kidney contributes importantly to acid-base balance by: 1) reabsorption of filtered bicarbonate and by 2) net acid excretion. Recent studies in our laboratory have elucidated mechanisms by which these two distinct processes are regulated. New concepts regarding the role of ammonium transport, the most highly regulated component of net acid excretion, and its role in acid-base homeostasis have emerged. Moreover, the impact of potassium balance on ammonium excretion has been elucidated from our studies of chronic hyperkalemia. In addition, we have explored and described defects in urinary acidification in a wide variety of models of distal renal tubular acidosis. The long term objectives of this proposed series of studies is to extend our examination of the pathophysiology of the acidification defects in renal tubular acidosis and hyperkalemia to the cellular and molecular level. To accomplish this goal we will employ microperfusion techniques in isolated rat inner medullary collecting ducts (IMCD) perfused in vitro, and papillary micropuncture in vivo to investigate the impact of chronic hyperkalemia, ureteral obstruction and chronic vanadate administration on proton secretion by the IMCD as measured by bicarbonate and ammonium transport. The relatively specific inhibitors, bifilamycin and SCM 28080, of the two types of proton pumps, H+ - ATPase, and H+ -K+ ATPase, respectively, will be used to determine the role of these pumps in defects of acidification. Secondly, we will determine if cortical and medullary collecting ducts and both IMCD and RCCT cells in culture express messenger RNA for the H+ -K+ ATPase, and if expression of this pump is modulated by acid base and potassium homeostasis.