Dissociative effects of piretanide on proximal tubular PO4 and HCO3 transport.
The effect of piretanide on renal electrolyte transport was evaluated by simultaneous micropuncture and clearance studies. In chronically thyroparathyroidectomized (TPTX) dogs, the drug caused an increased percentage excretion (%E) of sodium (from 0.6 +/- 0.1 to 15.2 +/= 1.8%, P less than 0.01) as well as of calcium (from 1.0 +/- 0.2 to 17.8 +/- 1.7%, P less than 0.001) and bicarbonate (from 1.2 +/- 0.4 to 5.9 +/- 0.9, P less than 0.001), but there was no change in %E of phosphate (4.0 +/- 0.9 to 6.6 +/- 1.6, P less than 0.10). In the presence of a constant infusion of parathyroid hormone (PTH) the drug caused a greater degree of natriuresis, calciuria, and bicarbonaturia and a significant increase in %E of PO4 (from 7.4 +/- 1.6 to 20.0 +/- 2.1, P less than 0.05). Proximal fractional reabsorption (PFR) of PO4 was unaffected, but there was a significant decrease in PFR of sodium, calcium, and bicarbonate in the TPTX dogs. The presence of PTH did not alter the effects of piretanide on PFR of phosphate and bicarbonate. There was no change in urinary or tubular fluid pH in either group of dogs. These data indicate that piretanide dissociates proximal PO4 transport from that of sodium and bicarbonate. In the presence of PTH, the drug inhibits PO4 transport beyond the late proximal convoluted tubule. In addition, tubular (and urinary) pH appears to be an important regulator of PO4 transport, especially in the absence of PTH.
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate; D007011:Hypoparathyroidism / Q000503:physiopathology; D007037:Hypothyroidism / Q000503:physiopathology; D007540:Isonipecotic Acids / Q000494:pharmacology*; D007668:Kidney / Q000503:physiopathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D010892:Pirinitramide / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism
D001639:Bicarbonates; D007540:Isonipecotic Acids; D010710:Phosphates; D010892:Pirinitramide; D012964:Sodium; D002118:Calcium