Converting-enzyme inhibitor administration lowers urinary free 19-nor-deoxycorticosterone levels.
19-Nor-deoxycorticosterone (19-nor-DOC) is a human mineralocorticoid. The regulation of its secretion is poorly understood, as renin angiotensin II (ANG II) stimulation has minimal effects on 19-nor-DOC. This study sought to determine if ANG II inhibition would decrease 19-nor-DOC production. Six normal subjects on fixed electrolyte intake were admitted to a metabolic unit. After a 5-day control period to establish electrolyte balance, enalapril, p.o., 10 mg/day, was administered for 28 days. This treatment resulted in ANG II inhibition, which was reflected by a rise in plasma renin activity, a blunting of the postural plasma aldosterone increment, and a decrease in aldosterone secretion rate (ASR). Levels of urinary free (UF) 19-nor-DOC progressively decreased from 294 +/- 108 ng/day on Day 0 to 164 +/- 70 on Day 3, 141 +/- 62 on Day 7, 101 +/- 38 on Day 14, 68 +/- 18 on Day 21, and 106 +/- 31 on Day 28. The decrease in 19-nor-DOC levels was synchronous with the fall in ASR (R = 0.94, n = 5, p less than 0.005), but it was of greater magnitude (71% decrease in 19-nor-DOC levels versus 41% decrease in ASR). In addition, the decrease in 19-nor-DOC levels correlated with a fall in urinary potassium and an increase in both urinary sodium and chloride (R = 0.68, -0.79, -0.87 respectively; n = 6, p less than 0.05). The fall in ASR, on the other hand, was not significantly correlated with the changes in these urinary electrolyte levels (R = 0.65, 0.64, 0.57 respectively; n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)
Griffing
G T
GT
Wilson
T E
TE
Melby
J C
JC
D000328:Adult; D000450:Aldosterone / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors; D003404:Creatinine / Q000652:urine; D003900:Desoxycorticosterone / Q000031:analogs & derivatives* / Q000652:urine; D004151:Dipeptides / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D004573:Electrolytes / Q000097:blood / Q000652:urine; D004656:Enalapril; D005260:Female; D006801:Humans; D008297:Male; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D004573:Electrolytes; D000804:Angiotensin II; C013282:tetrahydroaldosterone; D003900:Desoxycorticosterone; C019026:19-nordeoxycorticosterone; D000450:Aldosterone; D004656:Enalapril; D003404:Creatinine; D012083:Renin