Uncoupling of proximal sodium bicarbonate from sodium phosphate transport by bumetanide.
Re-collection micropuncture of late proximal tubular segments and simultaneous clearance studies were performed in chronically thyroparathyroidectomized dogs before and after the intravenous administration of bumetanide. The drug, a new sulfonamide-derivative diuretic, inhibited proximal fractional sodium and fluid transport by 0.12 (from 0.44 +/- 0.04 to 0.32 +/- 0.04, P less than 0.05) and that of bicarbonate by 0.14 (from 0.43 +/- 0.05 to 0.29 +/- 0.07, P less than 0.02). Tubular fluid bicarbonate concentration was unchanged, indicating a reduction in the transport of this ion proportionate to that of tubular fluid. However, unlike sodium and bicarbonate reabsorption, fractional proximal phosphate transport was unaltered (from 0.65 +/- 0.04 to 0.62 +/- 0.04, P greater than 0.40). The drug induced a substantial natriuresis; the percentage of filtered sodium excreted rose from 0.4 +/- 0.1 to 13.1 +/- 2.4% (P less than 0.005). Bicarbonate and phosphate excretion rose more modestly: the percentage excretion of the former ion increased from 0.9 +/- 0.3 to 3.7 +/- 0.08% (P less than 0.005) and that for phosphate doubled (from 3.4 +/- 1.0 to 6.8 +/- 1.3%, P less than 0.025). However, urinary pH did not change. Accordingly, bumetanide uncoupled the transport of sodium bicarbonate from that of sodium phosphate in the proximal convoluted tubule. It is concluded from these data that the action of bumetanide in the proximal convoluted tubule is probably not related either to carbonic anhydrase inhibition or to the impairment of sodium-phosphate-linked transport.
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002034:Bumetanide / Q000494:pharmacology*; D004232:Diuretics / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006439:Hemodynamics; D007668:Kidney / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D009318:Natriuresis; D010280:Parathyroid Glands / Q000502:physiology; D010710:Phosphates / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013965:Thyroidectomy
D001639:Bicarbonates; D004232:Diuretics; D010710:Phosphates; D002034:Bumetanide; D012964:Sodium