AJP - Endocrinology and Metabolism, Vol 243, Issue 4 265-E271, Copyright © 1982 by American Physiological Society
Inhibition of 25-hydroxyvitamin D3-1-hydroxylase by chronic metabolic acidosis
G. S. Reddy, G. Jones, S. W. Kooh and D. Fraser
Chronic metabolic acidosis had been shown to influence the renal metabolism
of 25-hydroxyvitamin D3. Using the isolated perfused rat kidney model, we
evaluated the rates of synthesis of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]
in vitamin D-depleted [D(-)] and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3]
in vitamin D-replete [D(+)] rats. Metabolic acidosis was induced in both
groups of rats by feeding aqueous ammonium chloride for 9 days. Kidneys
isolated from D(-) acidotic rats (mean pH, 7.11) exhibited a decreased rate
of 1,25(OH)2D3 synthesis (0.79 +/- 0.17 pmol produce . h-1 . g kidney-1)
when compared with that (1.27 +/- 0.09) of D(-) nonacidotic (mean pH, 7.33)
rats. There was a significant negative linear correlation between the rate
of synthesis of 1,25(OH)2D3 and the hydrogen ion concentration of the
animal (r = 0.79, P less than 0.005). The rate of synthesis of 24,25(OH)2D3
by the kidneys from D(+) acidotic (mean pH, 7.06) and nonacidotic (mean pH,
7.39) rats did not differ (0.81 +/- 0.21 vs. 0.60 +/- 0.12 pmol product .
h-1 . g kidney-1). It is concluded that chronic acidosis suppressed
1-hydroxylase activity, but does not suppress 24-hydroxylase activity.
