We propose to continue the investigation of how nephrotoxic heavy metals affect the mammalian kidney, and in particular, how they cause aminoaciduria. Because of significant environmental and occupational exposure to metals, this constitutes an important health problem. The work involves measurement of the kinetics of amino acid reabsorption from the glomerular filtrate in the intact rabbit, using both control animals and animals exposed to nephrotoxic heavy metals such as Hg, Cd, or Ni. The procedure to be employed has been developed in this laboratory and measures the fractional reabsorption of filtered solute, the size if the cortical transport pool, and the transepithelial transit times of isotopically labeled amino acids. The effect of metal exposure on the ability of isolated brush border membranes to transport amino acids will also be studied in an attempt to explain the kinetics of metal inhibition observed in vivo. Additional questions are 1) Do different metals exert identical effects on amino acid reabsorption? If not, then the possibility of interaction between metals will be investigated, a subject of importance because human exposure often may involved more than one metal. 2) Do metals interact with tubular epithelium at sites other than the brush border membrane? 3) To what extent does the damage caused by acute injection of metals resemble that more commonly seen following chronic low level exposure? 4) What is the relationship of the renal damage caused by Cd to the size of specific tissue compartments of this metal in the renal cortex?
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