ROLE OF NATRIURETIC FACTORS IN MINERALOCORTICOID ESCAPE PHENOMENON IN PATIENTS WITH PRIMARY ALDOSTERONISM

Abstract

The withdrawal effect of spironolactone treatment on natriuresis was studied in relation to atrial natriuretic peptide (ANP) and digitalis-like substance (DLS) in 5 patients with primary aldosteronism due to adrenal adenoma. The patients had been treated with spironolactone for 2-3 months before they were admitted. After admission, blood pressure, body weight and urinary excretion of DLS and sodium were measured daily. Venous sample were obtained twice a week for measurements of plasma renin activity (PRA) and plasma levels of aldosterone, ANP and DLS. Plasma volume was determined by radioisotope dilution using 125I-human serum albumin during the control period and on the 13th day after stopping spironolactone. The study was performed for 7 days during the treatment with spironolactone and for 18 days after stopping the administration. Urinary sodium excretion decreased initially and returned to the control levels successively. Body weight and plasma volume increased, and blood pressure rose steadily. PRA decreased markedly (p <0.05) from 2.1 ± 0.6 ng/ml/hr on the control days to 0.2 ± 0.1 ng/ml/hr on the 8 th day after stopping spironolactone. Plasma levels of aldosterone was 387± 150 pg/ml on the control days and did not change significantly after the withdrawal (278 ± 94 pg/ml on the 17th day). Plasma ANP levels increased significantly (p<0.05) from 26 ± 4 pg/ml on the control days to 195 ± 47 pg/ml on the 13th day ; however, plasma and urine levels of DLS decreased significantly (p <0.05). The data of the urinary sodium excretion showed the escape from sodium-retaining effect of aldosterone, and this escape could be explained by the increase in plasma ANP but not by the changes in DLS.