Antinatriuretic and kaliuretic activities of the reduced derivatives of aldosterone

Endocrinology. 1983 May;112(5):1852-6. doi: 10.1210/endo-112-5-1852.

Abstract

The mineralocorticoid activities of the two dihydro- and the four tetrahydroisomers of the ring A-reduced derivatives of aldosterone were tested in adrenalectomized male rats. Potency was assessed by three criteria. Overall mineralocorticoid activity is expressed as the ability to reduce the urinary Na+/K+ ratio; antinatriuretic activity is represented by decreases in urinary Na+/creatinine; kaliuretic activity is shown by increases in K+/creatinine. All measurements were made on urine collected in the period 1-3 h postinjection. Measurements of overall activity indicate that the potency of aldosterone is greater than 5 alpha-dihydroaldosterone (DHA) greater than 3 alpha, 5 alpha-tetrahydroaldosterone (THA) greater than 3 alpha, 5 beta-THA greater than 3 beta, 5 alpha-THA greater than 5 beta-DHA greater than 3 beta, 5 beta-THA. Measurements of individual cation effects indicated that reduced derivatives generally, and the 5 alpha-reduced derivatives in particular, have greater antinatriuretic than kaliuretic activity. For example 5 alpha-DHA possesses between 7% and 17% of the antinatriuretic activity of aldosterone but only 0.7-2.7% of the kaliuretic activity. 5 alpha-DHA and 3 alpha, 5 beta-THA at concentrations of 10(-7)M were also shown to have mineralocorticoid activity in the isolated toad bladder; both caused an increase in the short circuit current across this epithelium although not to the level shown by a similar concentration of aldosterone. 5 beta-DHA appeared to be inactive at this dose.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenalectomy
  • Aldosterone / analogs & derivatives*
  • Aldosterone / pharmacology*
  • Animals
  • Bufo marinus
  • Kinetics
  • Male
  • Oxidation-Reduction
  • Potassium / urine*
  • Rats
  • Rats, Inbred Strains
  • Sodium / urine*
  • Structure-Activity Relationship
  • Urinary Bladder / drug effects
  • Urinary Bladder / metabolism

Substances

  • Aldosterone
  • Sodium
  • Potassium