The response of the colon to
aldosterone is believed to be an important adaptive mechanism to excessive
sodium losses in
diarrhea. However, the degree to which
mineralocorticoid activity actually influences fecal output of
sodium in people with
diarrhea is unknown. To gain insight into this question, 10 normal people were treated with placebo,
fludrocortisone (an
aldosterone agonist), and
spironolactone (an
aldosterone antagonist) during three experimental periods lasting nine days. On days 5-8,
diarrhea was induced by ingestion of
phenolphthalein. Diet was controlled. Fecal
sodium was 40 meq/day on placebo and 29 meq/day on
fludrocortisone, consistent with
mineralocorticoid stimulation of intestinal
sodium absorption. However, contrary to our expectations,
spironolactone therapy was also associated with a fall in fecal
sodium output, to 28 meq/day. To explain this paradoxical effect of
spironolactone, we suggest that
sodium depletion caused by
spironolactone's natriuretic action on the kidney caused the release of an unknown stimulant of intestinal
sodium absorption, whose action more than overcame the reduced colonic absorption resulting from inhibition of
aldosterone activity by
spironolactone. This interpretation implies that the intestinal adaptation to
sodium depletion in
diarrhea involves both
aldosterone and an
aldosterone independent factor, working in concert to reduce fecal
sodium output.