PHOSPHATURIC EFFECT OF L-NMMA IN THE PRESENCE OF PARATHYROID-HORMONE

The objective of this study was to examine the effect of N-G-monomethy l-L-arginine (L-NMMA) on phosphate excretion in the presence and absen ce of parathyroid hormone (PTH). Renal clearances were obtained before and during infusion of L-NMMA (15 mg/kg bolus and 500 mu g . kg(-1). min(-1) infusion) in Sprague-Dawley rats with intact parathyroid gland s (n = 6), in thyroparathyroidectomized (TPTX) rats receiving a consta nt infusion of PTH-(1-34) (0.01-0.03 U . kg(-1). min(-1)) (n = 11) thr oughout the experiment, or in TPTX rats that received an acute infusio n of PTH-(1-34) (33 U/kg bolus and 1 U . kg(-1). min(-1) infusion) aft er L-NMMA infusion alone (n = 7). In rats with intact parathyroid glan ds, L-NMMA increased the fractional excretions of phosphate (FE(Pi)) a nd sodium (FE(Na)) and mean arterial pressure (MAP) (Delta 8.6 +/- 1.5 %, Delta 0.62 +/- 0.1%, and Delta 26.7 +/- 4.9 mmHg, respectively; P < 0.05). In TPTX rats receiving a constant infusion of PTH, L-NMMA agai n increased FE(Pi), FE(Na) and MAP (Delta 9.5 +/- 3.6%, Delta 1.1 +/- 0.4%, and Delta 28.4 +/- 4.5 mmHg, respectively; P < 0.05). However, i n TPTX rats, L-NMMA alone did not increase FE(Pi) (Delta 0.9 +/- 0.3%) , whereas the subsequent infusion of PTH with L-NMMA increased FE(Pi) (Delta 15.6 +/- 3.1%; P < 0.05). In an additional group of intact and TPTX rats, the fractional excretion of lithium (FE(Li)) was measured a s an index of proximal reabsorption. L-NMMA increased FE(Li) in intact rats (Delta 13.2 +/- 2.6%; P < 0.05), but not in TPTX rats (Delta 4.2 +/- 3.3%). In conclusion, L-NMMA increases phosphate excretion in ass ociation with increases in MAP and FE(Na), and this phosphaturic effec t is dependent on the presence of PTH.