Volume-pressure relationships during development of mineralocorticoid hypertension in man.

Serial measurements of urinary sodium excretion, sodium space, plasma volume, and plasma renin concentration were made during the development of hypertension in patients who were exposed to an excess of endogenous or exogenous mineralocorticoid activity. Five patients with primary aldosteronism due to adenoma were followed during spironolactone treatment, for 35-55 days after the drug had been stopped, and finally, after surgery. Blood pressure rose continuously after stopping spironolactone. Sodium balance, however, showed an initial phase of sodium gain, followed by a phase of gradual sodium loss. Sodium space and exchangeable sodium rose by 5.0 +/- 0.48 liters/1.73 m2 of body surface area (BSA) (P less than 0.005) and by 865 +/- 97 mEq/1.73 m2 BSA (P less than 0.005), respectively; the values were maximal after 10-15 days, declined afterward, but remained higher than during spironolactone treatment. Plasma and blood volumes rose by 624 +/- 90 ml/1.73 m2 BSA (P less than 0.005) and by 327 +/- 74 ml/1.73 m2 BSA (P less than 0.01), respectively; they were maximal after 20-25 days, and then returned to their initial values. Exchangeable sodium, during the phase of sodium loss, was inversely correlated with the rise in blood pressure (P less than 0.01). Renin fell during the phase of sodium gain, and remained low afterwards. Blood pressure and sodium space declined after surgery, but plasma volume showed no change. The postsurgery values of these parameters were not significantly different from those measured during spironolactone treatment. Two subjects with adrenocortical insufficiency, who were followed for 45-60 days during treatment with dexamethasone and 9alpha-fluorocortisol acetate, also showed a transient rise in sodium space and plasma volume. The results suggest a redistribution of body fluids during development of hypertension. They also suggest that the tendency of body fluid volumes to return to normal is pressure-dependent. The long-term effects of mineralocorticoid excess on the interrelations between pressure, volume, and renin bear some resemblance to the pattern observed in patients with established essential hypertension, i.e., pressure remains elevated despite a decrease of volume, and renin is "inappropriately" suppressed in relation to the sodium and volume status.