Does the kidney 'escape' from the kaliuretic action of mineralocorticoids?
The purpose of this study was to determine if there are renal mechanisms which limit the magnitude of potassium loss during mineralocorticoid-induced hypokalemia. To study the renal effects of mineralocorticoids in vivo, the 'cortical distal nephron' transtubular [K] gradient (TTKG) was calculated by dividing the urine [K] by the urine to plasma osmolality ratio; this in turn was divided by the arterial plasma [K]. Hypokalemia (2.6 +/- 0.1 mM) was induced in rabbits by the daily administration of 5 mg deoxycorticosterone acetate (DOCA) for 9-13 days. Infusion of a K-free isotonic solution into these rabbits resulted in more severe hypokalemia (1.6 +/- 0.1 mM) and a TTKG of 4.3 +/- 0.3. The subsequent infusion of a 60-mM K-containing solution elevated the plasma [K] to 5.1 +/- 0.1 mM and was associated with a significant rise in the TTKG to 5.9 +/- 0.4 (p less than 0.05). A K-free solution was then infused to lower the plasma [K]; when the plasma [K] fell below 4 mM, the TTKG decreased to 4.4 +/- 0.3 (p less than 0.05), and was equal to the preinfusion value. Thus, DOCA-induced hypokalemia diminishes renal K excretion by two mechanisms: first, the lower value for the denominator of the TTKG (the plasma [K]) results in a lower luminal [K] at a given TTKG. Second, the TTKG fell during hypokalemia and thereby decreased the luminal [K] in the cortical distal nephron. Hence the urinary K excretion rate was diminished to a greater extent than that predicted from the fall in the plasma [K] despite continuing mineralocorticoid action.
Zettle
R M
RM
Department of Medicine, St. Michael's Hospital, Toronto, Ont., Canada.
West
M L
ML
Chen
C B
CB
Halperin
M L
ML
D000818:Animals; D003900:Desoxycorticosterone / Q000494:pharmacology*; D005260:Female; D006929:Hyperaldosteronism / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011188:Potassium / Q000097:blood / Q000652:urine*; D011817:Rabbits
D003900:Desoxycorticosterone; D011188:Potassium