Effect of acid-base status on renal excretion and accumulation of lead in dogs and rats
Victery, W.; Vander, A.J.; Mouw, D.R.
American Journal of Physiology 237(5): F398-F407
1979
ISSN/ISBN: 0002-9513 PMID: 495756 Document Number: 140226
The relative roles of glomerular filtration, tubular reabsorption, and tubular secretion in renal handling and accumulation of Pb were evaluated in dogs and rats in varying acid-base status. Clearance of ultrafilterable Pb was measured in pentobarbital-anesthetized dogs and compared to creatinine clearance; plasma ultrafilterable Pb was estimated in vitro. Fractional (excreted/filtered) excretion of Pb was lowest in dogs undergoing metabolic acidosis, highest during metabolic alkalosis, and intermediate in dogs with normal acid-base status. Fractional excretion of Pb during metabolic alkalosis varied with Pb dose; net reabsorption occurred at higher doses and net secretion at lowest doses. Acetazolamide, which alkalinizes the urine in the absence of systemic alkalosis, failed to increase Pb excretion; this suggests that plasma pH (rather than urine pH) may be the important regulator of renal Pb transport. Pb accumulation via the luminal or basolateral membrane was assessed by comparing Pb content of the 2 kidneys when 1 was made nonfiltering (ureteral occlusion during mannitol diuresis). Alkalosis increased Pb entry into the kidney across both the basolateral and, via subsequent reabsorption of secreted Pb, the luminal membrane. Alkalosis evidently stimulates Pb secretion, which leads to increased basolateral uptake of Pb, which leads to increased accumulation and secretion. After acute administration of 203Pb to conscious rats, both Pb excretion and renal Pb content were elevated by alkalosis. Acutely induced alkalosis in chronically Pb-exposed rats also increased Pb excretion. Acute experiments with 203Pb are at least qualitatively relevant to the renal handling of chronically assimilated Pb.