INTERACTION OF THE RENAL NERVES AND PROSTAGLANDINS ON THE PHOSPHATURIC RESPONSE TO PTH IN PHOSPHATE-DEPRIVED RATS

Previous studies demonstrated that catecholamines modulate the phosphaturic response to parathyroid hormone (PTH) in normal rats. The present study was performed to determine the effect of unilateral renal denervation (DNX) and the interaction with prostaglandin synthesis on the blunted phosphaturic response to PTH in phosphate-deprived rats. One week before the acute experiment, rats were anesthetized, and the left kidney was denervated or sham surgery was performed. Rats were fed either a low-phosphate diet (LPD, 0.07%) or a normal-phosphate diet (NPD, 0.7%) for 2 days before the experiment. All rats were thyroparathyroidectomized (TPTX). Control clearances were taken from the left kidney 2 h after TPTX. PTH (33 U/kg + 1 U . kg(-1) . min(-1)) was infused for 45 min, and then the urine collections were repeated. In phosphate-deprived rats with an innervated kidney, PTH infusion resulted in a blunted phosphaturic response [changed fractional excretion of phosphate (Delta FE(Pi)) of 9.2 +/- 3.7%, n = 9] compared with rats fed NPD (Delta FE(Pi) 45.7 +/- 9.3%, n = 6) or those in the phosphate-deprived group with renal DNX (Delta FE(Pi) 23.6 +/- 5.0%, n = 12). Indomethacin pretreatment (3 mg/kg) markedly attenuated the phosphaturic response to PTH in phosphate-deprived rats with a denervated kidney (Delta FE(Pi), 3.2 +/- 1.3%, n = 7) but not in animals fed an LPD with innervated kidneys or in rats fed an NPD. Infusion of Iloprost (2 ng . kg(-1) . min(-1)), a stable prostaglandin I-2 analogue, in indomethacin-treated phosphate-deprived rats enhanced the phosphaturic response to PTH in rats with a denervated kidney (Delta FE(Pi) 17.3 +/- 3.5%). The present studies demonstrate that unilateral renal DNX enhances the phosphaturic response to PTH in phosphate-deprived rats and that this effect requires the presence of intact prostaglandin synthesis.