Pharmacological activity of calcimimetic NPS R-568 administered intravenously in rats: dose dependency.
Journal Title: Pharmacological Reports - Year 2006, Vol 58, Issue 4
Abstract
Calcimimetics administered orally cause "pharmacological parathyroidectomy" confirmed by a decrease in parathyroid hormone secretion (PTH) and in plasma Ca(2+) concentration. Parathyroidsare 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.
Authors and Affiliations
Apolonia Rybczyńska, Konrad Boblewski, Artur Lehmann, Czesława Orlewska, Henryk Foks
Keywords
Related Articles
- EP ID EP112825
- DOI -
- Views 91
- Downloads 0
Comparative study of multiple dosage of quercetin against cisplatin-induced nephrotoxicity and oxidative stress in rat kidneys.
Quercetin, a typical bioflavonoid ubiquitously present in fruits and vegetables, is considered to be helpful for human health. Cisplatin (cDDP) is one of the most active cytotoxic agents in the treatment of a wide range...
Effects of neurosteroids on the human corticotropin-releasing hormone gene.
Increased activity of hypothalamic-pituitary-adrenal (HPA) axis and hypersecretion of corticotropin-releasing hormone (CRH) are known to be important factors in pathogenesis of some stress-related diseases. Some neuroste...
Gabapentin synergistically interacts with topiramate in the mouse maximal electroshock seizure model: an isobolographic analysis.
The anticonvulsant effects produced by topiramate (TPM) and gabapentin (GBP) - two second-generation antiepileptic drugs, in numerous fixed-ratio combinations of 8:1, 4:1, 2:1, 1:1, 1:2, 1:4 and 1:8 were examined by isob...
Effects of 2-chloroadenosine on cortical epileptic afterdischarges in immature rats.
Adenosine may represent an endogenous anticonvulsant in the brain. This study focused on the possible anticonvulsant action of an adenosine agonist, 2-chloroadenosine, against cortical epileptic afterdischarges (ADs) in...
Role of adrenal gland hormones in antiinflammatory effect of calcium channel blockers.
Effects of amlodipine, lacidipine and nicardipine on acute phase of inflammation in the carregeenan model in intact rats were investigated in this study. In addition, the most effective dose of nicardipine that had the h...