MECHANISM OF RENAL ACID/BASE HOMEOSTASIS

肾脏通过以下方式对酸碱平衡做出重要贡献：

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.