Mineralocorticoid-induced blood pressure, electrolyte, and hormone changes, and reversal with spironolactone, in healthy men

Abstract

The pathophysiology of mineralocorticoid-induced hypertension is not clear, and the factors determining renal “escape” remain to be defined. In an attempt to clarify these unknowns, the effect of 9-alpha-fludrocortisone on blood pressure was studied in six healthy males on fixed sodium and potassium intakes. Systolic blood pressure increased by 10 mm Hg after 10 days of fludrocortisone therapy, and supine mean pressure rose by 6 mm Hg. During fludrocortisone administration, the increments of systolic blood pressure in individual subjects were negatively correlated with weight gained, the amount of sodium retained, and the degree of hypokalemia. Renal “escape” from the sodium-retaining influence of fludrocortisone was not determined by the amount of sodium retained, but was closely related to the rise in systolic blood pressure during the first 48 hr of treatment. A more pronounced rise in blood pressure was associated with earlier renal “escape”. Spironolactone therapy reversed the mineralocorticoid-induced abnormalities (increased body weight, rise in systolic blood pressure, fall in total body potassium, and decline in plasma renin concentration) in a dose-response manner. The results show that the hypertension resulting from fludrocortisone administration in normal man is not a function of expansion of the total body sodium content, and the renal “escape” appears to relate to the early development of hypertension rather than to the amount of sodium retained.