Previous work has focused on the acid-base and hemodynamic determinants of reabsorption in the rat proximal convoluted tubule (PCT). Factors that specifically affect sodium bicarbonate transport (e.g., luminal and peritubular bicarbonate concentrations/pH and luminal flow rate) have been differentiated from those that primarily alter sodium chloride reabsorption (e.g., peritubular [protein]). The mechanisms of these transport regulatory effects (whether on the active or passive transport components) have also been elucidated. Recently, free-flow micropuncture studies suggested marked axial heterogeneity of both bicarbonate and chloride transport in the PCT. The early PCT had an increased anion transport capacity and appeared to be regulated differently, exhibiting less inhibition by alkalemia on bicarbonate reabsorption but more flow-dependence for chloride reabsorption, compared to the late PCT. The present proposal is designed to extend previous investigations by examining the luminal and peritubular determinants of active and passive components of proximal bicarbonate and chloride reabsorption as a function of tubule length. In vivo microperfusion and free-flow micropuncture will be used to pursue the following specific purposes: (1) To determine whether the axial heterogeneity of anion transport in the PCT is an intrinsic property of the individual nephron segments or is a function of the axial profile of other luminal determinants or factors. (2) To compare the kinetics of selected luminal determinants, such as anion concentration and flow rate, on the active and passive components of bicarbonate and chloride reabsorption in the early and late PCT. (3) To quantitate and define the mechanism of the individual peritubular determinants, including [HCO3 ion]/pH, [protein], nerve activity and angiotensin II, on anion transport as a function of PCT length. (4) To examine and confirm the integrated effects of these determinants on early and late proximal reabsorption when several luminal and peritubular determinants of anion transport are simultaneously altered.
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