Altered fractional tetrahydroaldosterone excretion during pharmacological blockade and activation of the renin-aldosterone system.
Tetrahydroaldosterone (THA) is the principal metabolite and generally a good index of aldosterone secretion. This study undertakes the evaluation of the aldosterone secretion rate (ASR) and excretion of THA during pharmacological blockade and activation of the renin-aldosterone system. THA was measured by a simplified RIA and compared to ASR over a period of 28 days in 18 normotensive volunteers receiving either 1) a diuretic [hydrochlorthiazide (HCTZ), 50 mg/day], 2) an angiotensin-converting enzyme inhibitor (MK-421, 10 mg/day), or 3) combined therapy [HCTZ (50 md/day) plus MK-421 (10 mg/day)] in a metabolic unit on a controlled diet. Results of this study at 28 days indicate that 1) HCTZ, while producing secondary hyperaldosteronism, lowered the fractional THA excretion (defined as THA/ASR) (from 0.51 to 0.33; P less than 0.05); 2) MK-421 produced hypoaldosteronism and a slight increase in the THA/ASR (from 0.43 to 0.53; 0.05 less than P less than 0.01); 3) combined HCTZ and MK-421 resulted in a normalization of both aldosterone secretion and THA/ASR (from 0.51 to 0.50). In conclusion, HCTZ decreases the THA/ASR whereas MK-421 tends to increase it. Combined administration of HCTZ and MK-421 restores the THS/ASR to normal. Therefore, the determination of THA excretion can be an inaccurate index of aldosterone secretion when measured during either pharmacological blockade or activation of the renin-aldosterone system.
D000328:Adult; D000450:Aldosterone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides / Q000494:pharmacology; D004347:Drug Interactions; D004656:Enalapril; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology; D008297:Male; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012636:Secretory Rate / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D006852:Hydrochlorothiazide; C013282:tetrahydroaldosterone; C013283:tetrahydroaldosterone 3 beta-glucosiduronic acid; D000450:Aldosterone; D004656:Enalapril