Phosphaturic effect of L-NMMA in the presence of parathyroid hormone.

The objective of this study was to examine the effect of NG-monomethyl-L-arginine (L-NMMA) on phosphate excretion in the presence and absence of parathyroid hormone (PTH). Renal clearances were obtained before and during infusion of L-NMMA (15 mg/kg bolus and 500 micrograms.kg-1.min-1 infusion) in Sprague-Dawley rats with intact parathyroid glands (n = 6), in thyroparathyroidectomized (TPTX) rats receiving a constant infusion of PTH-(1-34) (0.01-0.03 U.kg-1.min-1) (n = 11) throughout the experiment, or in TPTX rats, that received an acute infusion of PTH-(1-34) (33 U/kg bolus and 1 U.kg-1.min-1 infusion) after L-NMMA infusion alone (n = 7). In rats with intact parathyroid glands, L-NMMA increased the fractional excretions of phosphate (FEPi) and sodium (FENa) 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 again increased FEPi, FENa, and MAP (delta 9.5 +/- 3.6%, delta 1.1 +/- 0.4%, and delta 28.4 +/- 4.5 mmHg, respectively; P < 0.05). However, in TPTX rats, L-NMMA alone did not increase FEPi (delta 0.9 +/- 0.3%), whereas the subsequent infusion of PTH with L-NMMA increased FEPi (delta 15.6 +/- 3.1%; P < 0.05). In an additional group of intact and TPTX rats, the fractional excretion of lithium (FELi) was measured as an index of proximal reabsorption. L-NMMA increased FELi 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 association with increases in MAP and FENa, and this phosphaturic effect is dependent on the presence of PTH.

Phosphaturic effect of parathyroid hormone in the spontaneously hypertensive rat.

The Okamoto spontaneously hypertensive rat (SHR) has been reported to have altered phosphate metabolism. Hypophosphaturia in the presence of increased serum parathyroid hormone (PTH) levels has been reported in the SHR. Therefore it has been postulated that the SHR may be hyporesponsive to the phosphaturic effect of endogenous PTH. In addition, the SHR exhibits enhanced renal sympathetic nerve activity. Recent studies demonstrated that stimulation of the renal adrenoreceptors decreases the phosphaturic response to PTH infusion. Thus a hyporesponsiveness to PTH in the SHR may be due in part to higher renal sympathetic tone. The present study determined the phosphaturic effect of a pharmacological dose of PTH (33 U/kg bolus and 1 U.kg-1.min-1 infusion) in the thyroparathyroidectomized SHR compared with its normotensive control, the Wistar Kyoto (WKY) rat. Three groups of clearance experiments were performed on male 10- to 14-wk-old SHR and WKY rats. In the first group of rats, the fractional excretion of phosphate (FEPi) in response to PTH infusion was 35.4 +/- 4.2% in the SHR (n = 6) and 26.2 +/- 3.0% in the WKY rat (n = 6), NS. In the second group, all animals underwent acute unilateral renal denervation (DNX). The FEPi in response to PTH was 35.3 +/- 1.5% in the innervated (INN) kidney of the SHR (n = 10) compared with 27.9 +/- 2.5% in the INN kidney of the WKY rat (n = 11), and 39.1 +/- 1.9% in the DNX kidney of the SHR compared with 30.5 +/- 2.0% in the DNX kidney of the WKY rat.(ABSTRACT TRUNCATED AT 250 WORDS)