The effect of spironolactone on sweat and urinary sodium excretion during exercise in humans

This study examined the effect of spironolactone on urinary (Na⁺]_urine) and sweat sodium concentration (Na⁺]_sweat) when controlling for sweat rate. Fifteen healthy subjects were required to complete two 90‐min exercise bouts (three 30‐min ordered exercise bouts at 60%, 70%, and 80% of the subjects’ age‐predicted maximum heart rate) in a 35°C and 40% relative humidity environmental chamber, once after administration of 300 mg spironolactone, and once after administration of 300 mg placebo. Both the drug and placebo were taken over an 18 h period, with the second 100 mg dose taken 6 h prior to exercise, and the first 200 mg dose taken 12 h prior to the second dose. Sweat rate was measured during each of the three exercise bouts using a Macroduct® sweat collector affixed to the flexor surface of the forearm. Urine sodium excretion rate was calculated for the three hour period immediately prior to each exercise bout. Urinary and sweat sodium concentrations were analyzed via flame photometry. Spironolactone had no effect on Na⁺]_sweat at the different sweat rates. However, the urinary sodium excretion rate was significantly higher with spironolactone use (P<0·05). These results demonstrate that spironolactone caused the expected natriuresis, but greater sodium excretion was not observed in the sweat gland. Since the mineralocorticoid receptors (MR) in the sweat gland were not antagonized by spironolactone in the same manner as those in the kidney, this suggests that different isoforms of the MR exist in the kidney and the sweat gland of humans.