RENAL REGULATION OF PHOSPHATE EXCRETION IN ENDOTOXAEMIC RATS

1. Maintenance of phosphate homeostasis is essential for energy produc ing and oxygen delivery systems, particularly, when the energy require ments are increased in certain conditions, such as septicaemia, We inv estigated the phosphaturic response to parathyroid hormone (PTH) in en dotoxin (ETx)-treated rats in order to clarify the renal regulation of phosphate excretion during endotoxaemia. 2. Wistar rats that had unde rgone thyroparathyroidectomy were challenged with either Escherichia c oli ETx (n = 8) or saline vehicle (n = 9), Thirty-minute renal clearan ce tests were done before and after PTH infusion, Rats infused with sa line instead of PTH served as time controls for the ETx- (n = 7) and s aline-treated (n = 8) rats. 3. In time control rats, ETx administratio n enhanced phosphate excretion progressively and this was associated w ith an obvious increase in the level of kidney adenosine 3 ',5 '-cycli c mono-phosphate (P < 0.005) compared with levels following saline veh icle administration, However, this phosphaturia in late-phase endotoxa emia was not observed in rats infused with PTH; ETx, but not saline ve hicle, 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 admin istration of the saline vehicle. 4. To test whether renal tubular sens itivity to parathyroid hormone related-protein (PTHrP) was enhanced du ring 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 se verity of the phosphaturia after PTHrP infusion was less in ETx- than in saline-treated rats. 5. In summary, although ETx administration cau ses a progressive increase in phosphate excretion in the absence of PT H, this is overcome by the antiphosphaturic effect of ETx, attenuating PTH-mediated phosphaturia after PTH infusion.