M. Vanburen et al., EFFECTS OF ACUTE MINERALOCORTICOID AND GLUCOCORTICOID RECEPTOR BLOCKADE ON THE EXCRETION OF AN ACUTE POTASSIUM LOAD IN HEALTHY HUMANS, The Journal of clinical endocrinology and metabolism, 77(4), 1993, pp. 902-909
To examine the role of mineralocorticoid and glucocorticoid in potassi
um (K) tolerance in healthy humans, we studied the effects of canrenoa
te, a mineralocorticoid antagonist, and RU486, a glucocorticoid antago
nist, on the excretion of a KCl load. Canrenoate (200 mg, iv) or RU486
(400 mg, orally) was administered 150 min before a KCl load (1 mmol/k
g BW, orally) in seven healthy males undergoing maximal water diuresis
. Clearance studies were extended for 5 h after the KCl load, and the
data were compared with time control, KCl load alone, and canrenoate a
lone. KCl increased K excretion (from 18.8 +/-2.4 to 63.3 +/- 3.9 mmol
/5 h; P < 0.01) and sodium (Na) excretion (from 35.9 +/- 2.1 to 72.9 /- 6.0 mmol/5 h; P < 0.01). Clearance calculations, based on maximal w
ater diuresis, were compatible with increased distal Na and volume del
ivery. Canrenoate alone modestly increased basal cumulative NaCl excre
tion and had no effect on K excretion. However, canrenoate blunted the
kaliuresis after the KCl load (51.9 +/- 4.4 mmol/5 h; P < 0.05 compar
ed to KCl alone) and stimulated natriuresis in a complementary way. Cl
earance data were compatible with diminished distal Na reabsorption an
d K secretion in response to an undisturbed KCl-induced increase in di
stal Na delivery. RU486 did not influence the excretion of the KCl loa
d or its effects on renal sodium handling parameters, although effecti
ve glucocorticoid receptor blockade was likely to be present in view o
f the increase in plasma cortisol. These data suggest that in healthy
humans, mineralocorticoid activity, but not glucocorticoid activity, i
s involved in the elimination of a K load. The latter contrasts with d
ata in adrenalectomized animals, in which situation glucocorticoid as
well as aldosterone are indispensible for normal K tolerance.