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| Titel: |
Effects of Cyclosporin A on Circadian Changes in Urinary Water, Sodium and Potassium Excretion in Conscious Unrestrained Chronically Cannulated Rats |
| Auteur: |
Pons, M. Mellado, M. Cambar, J. |
| Verschenen in: |
Biological rhythm research |
| Paginering: | Jaargang 28 (1997) nr. 1 pagina's 56-68 |
| Jaar: |
1997-02 |
| Inhoud: |
Cyclosporin A (CsA) is a potent immunosuppressive agent widely and successfully used to suppress organ rejection after transplantation. Unfortunately, its clinical use is hampered by a host of unwanted actions. The main adverse effect of CsA is its nephrotoxicity. In an effort to further examine CsA-induced renal dysfunction, the effects of CsA infused intravenously 6 hours long (10mg/kg/6hr) for 5 consecutive days to normal Sprague-Dawley rats (n=6), were investigated with specific emphasis on the circadian rhythms in water and electrolyte urinary excretion. Animals were individually housed in metabolism cages in a sound-damped room under constant conditions of temperature (21±1°C) and 12-hr light alternating with 12-hr dark (LD 12:12 8:00-20:00). Circadian changes in urinary excretion were determined over the 24-hr cycle collecting urine every 6-hr in unanesthetized, unrestrained, chronically cannulated rats in physiological control conditions on Day 0, under continuous infusion of saline solution at a constant rate. Diuresis, natriuresis and kaliuresis were subject to a circadian rhythmicity characterized by markedly increased values during the active dark phase of the animals, whereas the lowest values were detected during daytime. Afterwards, temporal variations were studied on Day 5 after 5 consecutive days of CsA infusion. As a consequence of CsA treatment, no circadian pattern could be detected either in water or in electrolyte urinary excretion. Moreover, the day-night differences were flattenned. Using an urinary enzyme (N-acetyl-ss-D-glucosaminidase) as a marker of tubular injury, CsA-induced renal damage could be evidenced. The study demonstrated that circadian rhythms in urinary water, sodium and potassium excretion were completely abolished under CsA treatment in normal rats. Such data lead to speculate about a presumable disturbance of endogenous kidney oscillators controlling the circadian excretory rhythmicity. |
| Uitgever: |
Taylor & Francis |
| Bronbestand: |
Elektronische Wetenschappelijke Tijdschriften |
Details van artikel 6 van 16 gevonden artikelen
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