An in vivo study of voltage-dependent renal tubular acidosis induced by amiloride.
It has been proposed that most forms of hyperkalemic distal renal tubular acidosis (dRTA) result from a voltage-dependent acidification defect in the cortical collecting tubule (CCT) in which hydrogen and potassium secretion are decreased secondary to a reduced, transepithelial potential difference (PD) arising from impaired sodium reabsorption. The present in vivo study examines one model of hyperkalemic dRTA, induced by chronic amiloride administration, to examine the relationship between urinary excretion of hydrogen and potassium ions and CCT PD in the rat kidney. Chronic administration of amiloride produced a significant metabolic acidosis with a plasma bicarbonate of 21.3 mmol/liter compared to 25.9 mmol/liter in control rats. Plasma potassium was higher in experimental animals (4.9 mmol/liter vs. 3.3 mmol/liter in controls) and was associated with a significantly reduced fractional excretion of potassium of 11.2% versus 37.4% in controls. When animals were loaded with DOCA and infused with 4% sodium sulphate to maximize urine acidification, urine pH was significantly higher in the experimental group (6.35 vs. 5.55 in controls) while the mean PD in cortical collecting tubules was markedly lower at -21.1 mV versus -58.9 mV in controls. These results support a voltage dependent mechanism to explain the defect in hydrogen and potassium ion secretion induced by amiloride.
Allen
G G
GG
Department of Medicine, Flinders Medical Centre, South Australia.
Barratt
L J
LJ
D000141:Acidosis, Renal Tubular / Q000139:chemically induced / Q000503:physiopathology*; D000584:Amiloride; D000818:Animals; D003900:Desoxycorticosterone / Q000494:pharmacology; D004573:Electrolytes / Q000097:blood / Q000652:urine; D004848:Epithelium / Q000502:physiology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007672:Kidney Cortex / Q000503:physiopathology; D007677:Kidney Function Tests; D007685:Kidney Tubules, Collecting / Q000503:physiopathology; D008297:Male; D008564:Membrane Potentials; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D004573:Electrolytes; D003900:Desoxycorticosterone; D000584:Amiloride