ISSN:
1432-0827
Keywords:
Vitamin D
;
Chronic uremia
;
Rats
;
Renal responsivity
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Medicine
,
Physics
Notes:
Summary Various investigators have shown that chronic uremia is associated with a normal or exaggerated phosphaturic response to parathyroid hormone (PTH). To explore the relationship between progressive uremia, renal tubular cyclic AMP (cAMP), and inorganic phosphate (Pi) response to PTH and acidosis, in vivo and in vitro experiments were designed in rats with experimental uremia of 4–6 weeks’ duration. Both uremic and pair-fed control rats were treated with 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and/or chronic NH4Cl feeding. Urinary Pi and cAMP and plasma immunoreactive PTH (iPTH) were measured as well as PTH- and NaF-stimulated cAMP from isolated renal tubules. Excretion of cAMP decreased by 30% in uremic as compared to control rats despite a 3-fold rise in Pi excretion. Acidosis superimposed on uremia did not further decrease cAMP excretion, nor did it significantly alter the elevated Pi excretion. 1,25(OH)2D3 treatment of uremic rats further lowered cAMP excretion although Pi excretion rose, hypercalcemia occurred, and plasma iPTH fell. In nonuremic control rats, 1,25(OH)2D3 treatment led to hypercalcemia, a progressive decrease in cAMP, and increase in Pi excretion. Isolated renal tubules from uremic or acidotic uremic rats revealed a 50% reduction in both PTH- and NaF-stimulated cAMP generation compared to control rat renal tubules. This observation was unchanged by 1,25(OH)2D3 treatment. Renal tubules of 1,25(OH)2D3-treated control rats demonstrated a decreased cAMP production in response to both PTH and NaF which was inversely related to the calcium content of the renal tubules. Renal tubular calcium levels of uremic rats, initially 3-fold elevated, also increased during 1,25(OH)2D3 treatment. These results are consistent with the hypothesis that progressive uremia results in a dissociation between PTH, urinary cAMP, and Pi excretion which cannot be explained by either metabolic acidosis or 1,25(OH)2D3 deficiency.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02408070
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