The effect of
hydroflumethiazide (HFT) on renal excretion of
sodium, chloride, and
potassium was studied in
congestive heart failure and related to urinary excretion of
thiazide and
aldosterone. HFT 75 or 150 mg was administered orally once daily for 4 days to 8 male patients with roentgenological evidence of
enlarged heart and slight or no peripheral oedema receiving digitalis and controlled diet. Urinary excretion of HFT did not change after repeated doses, whereas urinary excretion of a metabolite increased significantly. Initially, HFT induced a significant increase in the urinary excretion of
sodium and
potassium. After repeated doses, the
natriuretic effect declined gradually in 6 of the patients. There was consistently a small
natriuretic effect and a large kaliuretic effect at high serum
aldosterone concentrations and high urine
aldosterone excretion rates, whereas at low
aldosterone levels, there was a wide range in magnitude of these effects. Relationships of the log urinary excretion rate of HFT to the increase in urinary excretion rate of
sodium, chloride, and
potassium showed positive and significant correlations. It was concluded that reduced
natriuretic effect of HFT in
congestive heart failure is not due to reduced delivery of
thiazide to renal tubular cells but to compensatory adjustments of the kidney in part induced by
aldosterone.