The effect of dexamethasone on renal potassium excretion and acute potassium tolerance

In order to further characterize the kaliuretic action of dexamethasone, the effect of the hormone on renal electrolyteexcretion and potassium tolerance was evaluated. In the first set of experiments, dexamethasone was administered acutely to unreplaced adrenalectomized rats, to adrenalecto-mized rats replaced with a single daily injection of dexametha-sone (10 μg/100 g-day), and to intact control rats. After dexa-methasone injection (10 μxg/100 g), urinary potassium excretion increased by 105% in unreplaced adrenalectomized rats (0.99 ± 0.13 to 2.02 ± 0.26 Meq/min, P < 0.005) and by 59% in rats maintained on glucorticoid (0.87 ± 0.10 to 1.38 ± 0.18 (μeq/mm, P < 0.05). The kaliuresis in adrenalectomized rats was associated with a significant increase in phosphate excretion and by a tendency for urinary chloride excretion torise. In contrast, potassium excretion was unchanged by dexamethasone in control rats. These results indicate that the kaliuretic effect of dexamethasone is influenced by the degree of glucocorticoid deficiency before hormone administration. An additional study with K loading was performed in these same three groups of rats to evaluate the effect of dexamethasone replacement on potassium tolerance. Adrenalectomized rats maintained in daily dexamethasone replacement received an additional dose of hormone (50 μg/100 g) before study. After KC1, plasma potassium concentration rose significantly higher in unreplaced adrenalectomized rats vs. control (2.2 ± 0.2 vs. 1.3 ± 0.4 meq/liter, P < 0.05) and peak renal potassium clearance was significantly blunted (577 ± 90 vs. 1104 ± 120 μl/min, P < 0.001). This impairment in potassium tolerance could not be attributed to hypotension, acidemia, diminished urinary flow, or sodium delivery in the distal nephron in unreplaced adrenalec-tomized rats but may be explained by decreased renal perfusion since glomerular filtration rate at the end of study was lower than in controls. Dexamethasone replacement improved potassium tolerance (peak ΔP_k = 1.7 ± 0.1 meq/liter) and renalpotassium clearance (942 ± 60 μl/min). These data demonstrate that dexamethasone, at the high dose employedduring KC1 loading, improves renal potassium tolerance by enhancing renal K clearancein adrenalectomized rats. These results explain our previous report of near normal potassium excretion in glucocor-ticoid replaced adrenalectomized rats.