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 electrolyte excretion and potassium tolerance was evaluated. In the first set of experiments, dexamethasone was administered acutely to unreplaced adrenalectomized rats, to adrenalectomized rats replaced with a single daily injection of dexamethasone (10 micrograms/100 g X day), and to intact control rats. After dexamethasone injection (10 micrograms/100 g), urinary potassium excretion increased by 105% in unreplaced adrenalectomized rats (0.99 +/- 0.13 to 2.02 +/- 0.26 mueq/min, P less than 0.005) and by 59% in rats maintained on glucocorticoid (0.87 +/- 0.10 to 1.38 +/- 0.18 mueq/min, P less than 0.05). The kaliuresis in adrenalectomized rats was associated with a significant increase in phosphate excretion and by a tendency for urinary chloride excretion to rise. 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 micrograms/100 g) before study. After KCl, plasma potassium concentration rose significantly higher in unreplaced adrenalectomized rats vs. control (2.2 +/- 0.2 vs. 1.3 +/- 0.4 meq/liter, P less than 0.05) and peak renal potassium clearance was significantly blunted (577 +/- 90 vs. 1104 +/- 120 microliter/min. P less than 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 adrenalectomized 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 delta Pk = 1.7 +/- 0.1 meq/liter) and renal potassium clearance (942 +/- 60 microliter/min). These data demonstrate that dexamethasone, at the high dose employed during KCl loading, improves renal potassium tolerance by enhancing renal K clearance in adrenalectomized rats. These results explain our previous report of near normal potassium excretion in glucocorticoid replaced adrenalectomized rats.
D000315:Adrenalectomy; D000818:Animals; D002712:Chlorides / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004361:Drug Tolerance; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010710:Phosphates / Q000378:metabolism; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism
D002712:Chlorides; D010710:Phosphates; D003907:Dexamethasone; D012964:Sodium; D011188:Potassium