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Increase in plasma free fatty acids and natriuresis by xanthines may reflect adenosine antagonism

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Summary

The hypothesis has been examined that adenosine is involved in the diuretic and free fatty acid (FFA) — releasing action of xanthines. The effects of theophylline (T), a potent adenosine antagonist, were compared with those of enprofylline (3-propyl xanthine, E), which exerts negligible antagonism of adenosine. Eight healthy male volunteers were given E 1.5 mg/kg, T 5.0mg/kg or placebo 0.9% saline (P) intravenously in a double-blind, randomized, cross-over investigation. Blood samples were analyzed for E, T, catecholamines (CA: adrenaline, noradrenaline and dopamine), FFA, renin, glucose, glucagon and insulin, and urine was collected at 2-h intervals. T (plasma concentration 53±8 µmol/l) but not E (11±2 µmol/l) caused an increase in FFA from 0.42 to 0.86 mmol/l after 90 min. Without affecting the urinary excretion of potassium, T doubled natriuresis and the urine volume as compared to E and P. Neither T nor E had any effect on plasma CA, or on any other of the metabolic parameters studied. E, but not T, produced a small but statistically significant decrease in diastolic blood pressure (5 mmHg) and an increase in heart rate (3 beats/min). It is suggested that the difference between E and T in terms of stimulation of FFA-release and natriuresis may be related to their different ability to antagonize adenosine.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, University Hospital, Lund, Sweden

    K. -E. Andersson, N. Johannesson, B. Karlberg & C. G. A. Persson

  2. Department of Medicine, University Hospital, Linköping, Sweden

    B. Karlberg

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  1. K. -E. Andersson
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  2. N. Johannesson
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  3. B. Karlberg
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  4. C. G. A. Persson
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Andersson, K.E., Johannesson, N., Karlberg, B. et al. Increase in plasma free fatty acids and natriuresis by xanthines may reflect adenosine antagonism. Eur J Clin Pharmacol 26, 33–38 (1984). https://doi.org/10.1007/BF00546705

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  • DOI: https://doi.org/10.1007/BF00546705

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