NDT Advance Access originally published online on February 19, 2004
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Nephrol Dial Transplant (2004) 19: 1077-1082
Nephrol Dial Transplant Vol. 19 No. 5 © ERA-EDTA 2004; all rights reserved
Original Article
Effects of the adenosine A1 receptor inhibitor FK 838 on proximal tubular fluid output in rats
Institute for Basic Psychiatric Research, Department of Biological Psychiatry, Aarhus University Hospital, Denmark
Correspondence and offprint requests to: Dr Martin Bak, PhD, Department of Biological Psychiatry, Institute for Basic Psychiatric Research, Skovagervej 2, DK-8240 Risskov, Denmark. Email: mb{at}dadlnet.dk
Background. Adenosine A1 receptor blockade has been suggested as a treatment in conditions with sodium and fluid retention because it increases urinary Na+ excretion and increases proximal tubular fluid output. In the present study, we examine the time course for the renal responses to adenosine A1 receptor blockade in order to investigate whether the effects may be prolonged and not just temporary.
Methods. The acute effects of the adenosine A1 receptor inhibitor FK 838 on segmental tubular Na+ handling were examined by a renal clearance technique in conscious chronically instrumented rats. Lithium clearance (CLi) was used as a clearance marker of proximal tubular fluid output.
Results. Acute adenosine A1 receptor inhibition did not affect the glomerular filtration rate (GFR) significantly. In contrast, the inhibition led to significant increases in CLi (from 290±28 to 431±28 µl/min/100 g), fractional Li+ excretion (FELi) (from 33±2 to 47±3%) and fractional Na+ excretion (FENa) (from 0.44±0.07 to 2.03±0.42%). Sodium excretion, expressed as a fraction of proximal tubular fluid output (CNa/CLi), rose from 1.3±0.2 to 4.2±0.4%, suggesting that the natriuretic effect was supported by inhibition of distal nephron Na+ reabsorption. All values returned to baseline values during the clearance study and thereby indicated that neither proximal tubular fluid output nor urinary sodium excretion remained elevated for a prolonged time.
Conclusion. It is concluded that in conscious unstressed rats, acute adenosine A1 receptor inhibition by FK 838 led to a significant natriuresis that was caused by inhibition of proximal tubular Na+ reabsorption, possibly with a contribution from inhibition of distal nephron Na+ reabsorption. The increased proximal tubular fluid output and the increased urinary Na+ excretion returned to baseline values during the clearance study, indicating that none of these effects of adenosine A1 blockade were long lasting.
Keywords: adenosine A1; FK 838; tubulo-glomerular feedback
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