Aldosterone metabolism in rat renal tissue in vitro

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Abstract
In the present study the formation of lipid soluble metabolites from3H-aldosterone was investigated in vitro in isolated kidneys and kidney and liver slices of Sprague Dawley rats. The steroids were separated by HPLC (forward and reversed phase systems) and detected on-line as UV- or3H-chromatograms. Apart from an unenzymatically formed substance, isoaldosterone, three less polar metabolites were traced (A1, A2, A3). The structure of the quantitatively most important metabolite (A1), was identified as 5α-dihydroaldosterone using a combination of techniques such as chromatographic comparison with reference steroids, antibody binding and mass spectrometry. Evidence for further conversion of DHaldo to 3α,5α-tetrahydroaldosterone was obtained in chromatographic and antibody binding studies. The formation of metabolites was not dependent on glomerular filtration. Furthermore it displayed regional heterogeneity with highest activity in the outer medulla. Finally it was observed that the in vitro metabolism of aldosterone was not saturable over a range of initial aldo concentration of 10−9 to 10−5 M.