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. 1978 Dec;62(6):1325–1333. doi: 10.1172/JCI109253

Aldosterone Stimulation of Riboflavin Incorporation into Rat Renal Flavin Coenzymes and the Effect of Inhibition by Riboflavin Analogues on Sodium Reabsorption

Daniel Trachewsky 1,2,3
PMCID: PMC371898  PMID: 748381

Abstract

This study was designed to investigate a possible relationship between the effect of aldosterone upon urinary electrolytes and the incorporation of [14C]riboflavin into renal [14C]flavin mononucleotide (FMN) and [14C]flavin adenine dinucleotide (FAD). Adrenalectomized Sprague-Dawley rats that weighed between 185 and 210 g were pretreated with 15 μg/100 g body wt dexamethasone intraperitoneally. 16 h later they were administered aldosterone (1.5 μg/100 g body wt) and [14C]riboflavin (5.0 μCi/200 g body wt). The urethra of each rat was ligated, and the rats were sacrificed by decapitation 3 h later. The urine was aspirated from the bladders of each rat and analyzed for total Na+ and K+ excretion while the kidneys were removed and the formation of [14C]FMN and [14C]FAD was determined for each kidney. There was a significant increase in the formation of renal [14C]FMN and [14C]FAD (27.3 and 14.4%, respectively) after aldosterone treatment. Aldosterone significantly decreased the excretion of Na+ by 50%, and increased that of K+ by 55%.

To determine if the increased incorporation of [14C]riboflavin into renal [14C]FMN and [14C]FAD was an important intermediary step in the aldosterone-induced alterations in urinary Na+ and K+, the riboflavin analogues 7,8-dimethyl-10-formylmethyl isoalloxazine or 7,8-dimethyl-10-(2′-hydroxyethyl) isoalloxazine were given to the animals i.p. to diminish the conversion of riboflavin to FMN by competitively inhibiting the enzyme flavokinase (EC 2.7.1.26). These analogues were found to significantly counteract the decreased urinary excretion of Na+ as a result of aldosterone from 26±9% to 124±58% (SEM) with a dose-related response when administered from 10 to 25 μg/100 g body wt. The same doses of the analogues that significantly increased the urinary output of Na+ when administered simultaneously with aldosterone also significantly decreased the formation of renal [14C]FMN from 15±4 to 38±3% when compared with the effects of aldosterone alone. The analogues exerted no significant effect on the increased urinary excretion of K+ by aldosterone. The analogues alone had no influence on urinary Na+ and K+ output or the formation of renal [14C]FMN and [14C]FAD at the dose levels that we investigated.

These data strongly suggest that the enhanced synthesis of renal FMN and FAD may be a causative factor in the increased reabsorption of Na+ as a result of aldosterone; and, consequently, riboflavin analogues may function as a novel class of antimineralocorticoids.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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