Pharmacological activity of calcimimetic NPS R-568 administered intravenously in rats: dose dependency

Calcimimetics administered orally cause "pharmacological parathyroidectomy" confirmed by a decrease in parathyroid hormone secretion (PTH) and in plasma Ca(2+) concentration. Parathyroids are also the source of parathyroid hypertensive factor (PHF). The aim of this study was to determine the dose-dependent effect of an intravenously (iv) applied calcimimetic, NPS R-568, on plasma Ca(2+) concentration, urinary phosphate excretion and mean arterial blood pressure (MAP) in rats. Clearance experiments were performed on male Wistar rats anesthetized with thiopental and infused iv with saline supplemented with (3)H inulin for glomerular filtration rate (GFR) determination. NPS R-568 was administered iv as a bolus at the doses: 0.5, 1.0, 2.5 and 5.0 mg/kg. Control group of rats received vehicle only. MAP was monitored continuously in the carotid artery. Urine was collected from cannulated urinary bladder. NPS R-568 applied iv dose-dependently decreased plasma Ca(2+) and fractional phosphate excretion (FE(Pi)). In the control group, no significant changes in plasma Ca(2+) and FE(Pi) were observed. The most efficient hypotensive effect vs. control group was induced by the NPS R-568 of a dose of 1.0 mg/kg. Our results indicate that the dose of 1 mg/kg of the calcimimetic NPS R-568 administered iv is sufficient to induce the decrease in plasma Ca(2+) and urinary phosphate excretion accompanied with hypotensive effect in Wistar rats.