Aldosterone esters and the heart.
There are clinical and experimental situations in which symptoms of mineralocorticoid excess are remediable with mineralocorticoid receptor antagonist treatment, in spite of paradoxically low levels of plasma renin and aldosterone. Several decades ago, a factor isolated from the heart was described that had mineralocorticoid properties like those of aldosterone, but much more potent. It was thought to be similar to aldosterone-18-monoacetate or -21-monoacetate, acetyl derivatives of aldosterone that are very rapidly hydrolyzed in the circulation. In our efforts to confirm and extend these observations, we extracted rat hearts and plasma harvested in a manner that would minimize hydrolysis. The product was subjected to several forms of TLC and HPLC and compared to several acetylated derivatives of aldosterone standards. We found that 68% of the aldosterone extracted from fresh myocardium corresponded to an aldosterone derivative that migrates at the same rate as aldosterone-20-monoacetate. The identity of this compound awaits definitive analysis. Tritiated aldosterone-21-monoacetate hydrolyzed to form aldosterone very rapidly; negligible monoacetate remained in blood left at 37 degrees C for 5 min or in hearts left at room temperature for 30 min. Regulation of aldosterone production serves the requirements of fluid and electrolyte homeostasis provided by transport epithelia, primarily that of the kidney. Nonepithelial actions of aldosterone would be freed of these regulatory constraints if the formation of a more potent derivative of the parent compound to which it is almost immediately hydrolyzed in the circulation were regulated within the nonepithelial target tissues.
Gomez-Sanchez
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Division of Endocrinology, Montgomery VA Medical Center, The University of Mississippi Medical Center, Jackson 39216-4505, USA. cgomez-sanchez@medicine.umsmed.edu
Foecking
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MF
Gomez-Sanchez
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EP
D000450:Aldosterone / Q000031:analogs & derivatives* / Q000378:metabolism*; D000818:Animals; D001769:Blood / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004797:Enzyme-Linked Immunosorbent Assay; D004952:Esters; D006868:Hydrolysis; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D004952:Esters; C438685:aldosterone-20-acetate; C060976:aldosterone-21-acetate; D000450:Aldosterone