Antinatriuretic and kaliuretic activities of the reduced derivatives of aldosterone.
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.
D000315:Adrenalectomy; D000450:Aldosterone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D002024:Bufo marinus; D007700:Kinetics; D008297:Male; D010084:Oxidation-Reduction; D011188:Potassium / Q000652:urine*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000652:urine*; D013329:Structure-Activity Relationship; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism
D000450:Aldosterone; D012964:Sodium; D011188:Potassium