Effect of acute hypoxia on phosphate excretion in rats
Mimura, Y.; Knox, F.G.
American Journal of Physiology 266(2 Pt 2): R578-R583
1994
ISSN/ISBN: 0002-9513 PMID: 8141418 Document Number: 437709
This study evaluated the effect of acute hypoxia on renal handling of phosphate in rats in the presence and absence of parathyroid hormone (PTH). Hypoxia causes respiratory alkalosis in spontaneously breathing humans and animals. Respiratory alkalosis has been reported to induce a blunted phosphaturic response to PTH. In this study, to avoid the confounding effect of hypocapnia accompanying the hypoxia on phosphate excretion, the rats were ventilated mechanically, and arterial PCO-2 levels were controlled. Rats were divided into two main groups depending on the arterial PO-2 levels: a hypoxic group (n = 16) and a normoxic group (n = 18). Hypoxia was produced by ventilating with 10% oxygen, and hypocapnia was produced by hyperventilation. In response to PTH, the hypoxic rats without hypocapnia showed a greater increase in fractional excretion of phosphate (FE-P-i; 37.7 +- 2.6%, mean +- SE) compared with normoxic rats (27.4 +- 2.5%, P lt 0.02). During hypocapnia, there was no difference in FE-P-i between hypoxic and normoxic groups (21.2 +- 1.5 and 19.5 +- 1.2%, respectively), and both groups showed a significantly blunted phosphaturic response to PTH compared with normocapnia (P lt 0.05 and P lt 0.01, respectively). Urinary adenosine 3',5'-cyclic monophosphate (cAMP) increased similarly after PTH infusion between each group. To test whether the phosphaturic effect of PTH in hypoxia and the blunted phosphaturic effect of PTH in hypocapnia are due to steps beyond the generation of cAMP, the phosphaturic response to cAMP infusion was evaluated in 1) hypoxic and normocapnic rats (n = 6), 2) normoxic and normocapnic (control) rats (n = 6), and 3) normoxic and hypocapnic rats (n = 7). In response to cAMP infusion, the hypoxic rats exhibited a greater FE-P-i (30.0 +- 1.4%, P lt 0.05), while the hypocapnic rats showed a smaller FE-P-i (11.3 +- 1.8%, P lt 0.01) compared with control rats (24.1 +- 1.0%). We conclude that acute hypoxia is phosphaturic and enhances the phosphaturic effect of PTH and that this effect can be overridden by hypocapnia.