Renal regulation of phosphate excretion in endotoxaemic rats

1. Maintenance of phosphate homeostasis is essential for energy producing and oxygen delivery systems, particularly, when the energy requirements are increased in certain conditions, such as septicaemia. We investigated the phosphaturic response to parathyroid hormone (PTH) in endotoxin (ETx)-treated rats in order to clarify the renal regulation of phosphate excretion during endotoxaemia. 2. Wistar rats that had undergone thyroparathyroidectomy were challenged with either Escherichia coli ETx (n = 8) or saline vehicle (n = 9). Thirty-minute renal clearance tests were done before and after PTH infusion. Rats infused with saline instead of PTH served as time controls for the ETx- (n = 7) and saline-treated (n = 8) rats. 3. In time control rats, ETx administration enhanced phosphate excretion progressively and this was associated with an obvious increase in the level of kidney adenosine 3', 5'-cyclic mono-phosphate (P < 0.005) compared with levels following saline vehicle administration. However, this phosphaturia in late-phase endotoxaemia was not observed in rats infused with PTH; ETx, but not saline vehicle, blunted the PTH-mediated increase in phosphate excretion (P < 0.005). Increased urinary noradrenaline and constant dopamine excretion were observed in endotoxaemic rats. Endotoxin administration produced marked metabolic acidosis and hypocapnia in comparison with the administration of the saline vehicle. 4. To test whether renal tubular sensitivity to parathyroid hormone related-protein (PTHrP) was enhanced during endotoxaemia, phosphaturic response to PTHrP in ETx- (n = 7) and saline-treated rats (n = 7) was examined. Parathyroid hormone related-protein infusion produced phosphaturia in both groups. However, the severity of the phosphaturia after PTHrP infusion was less in ETx-than in saline-treated rats. 5. In summary, although ETx administration causes a progressive increase in phosphate excretion in the absence of PTH, this is overcome by the antiphosphaturic effect of ETx, attenuating PTH-mediated phosphaturia after PTH infusion.