Blocking by spironolactone (SC 9420) of the action of aldosterone upon the intestinal transport of potassium, sodium, and water.

Abstract

CardiffEDITORIAL COMMENT This study continues the work described in the previous paper and brings out another common factor concerning electrolyte transport.The action of the adrenal mineralocorticoids upon the intestinal mucosa closely resembles their effect upon the renal tubular epithelium (Shields, 1964). Thus, in both organs, the transfer of potassium into the lumen is stimulated by the intravenous administration of aldosterone (Barger, Berlin, and Tulenko, 1958;Shields, Mulholland, and Elmslie, 1966). Because the renal action of the mineralocorticoids can be blocked by the spironolactones (Bartter, 1960) the effect of these agents upon the intestinal action of aldosterone was investigated. METHODThe movement of potassium, sodium, and water into and out of the lumen of isolated segments of ileum (two dogs) and of colon (three dogs) was measured using the radioactive isotopes of sodium and potassium, and the stable isotope of water, deuterium oxide. Details of the preparation and of the experimental technique are given in the previous paper (Shields et al., 1966). TYPES OF EXPERIMENT In each dog, six types of experiment were performed: I Spironolactone alone One hundred mg. spironolactone SC 9420 (Aldactone, Searle) was given by mouth at 6.00 a.m. At 9.00 a.m. an intravenous infusion of 5 % (w/v) dextrose was set up and continued at a rate of 40 ml. per minute. Absorption tests, each lasting 10 minutes, were performed at 1, 2, 2j, 3i, 4, and 5 hours after the beginning of the dextrose infusion. One such experiment was performed in each dog.2 Spironolactone + aldosterone (high dose) The experimental technique was identical to (1), except that at 9.00 a.m., 250 pg. aldosterone (Aldocorten, Ciba) was injected intravenously and a further 250 ,tg. was added to the dextrose solution and delivered to the dog at a rate of 1 jig. per minute. One experiment of this type was performed on each dog.3 Spironolactone + aldosterone (low dose) The experi-'Present address:

Hormones and Water Movement Through the Vertebrate Intestine

“…Continuous infusion of aldosterone produces an increase in the secretion of potassium in both the ileum and colon of dogs as well as the colon of man [111]. This is similar to the effect of the hormone on the renal tubule and is similarly blocked by spirolactone [37]. One report has suggested that the bidirectional flux rates of both sodium and potassium through the small intestine of rats is increased by aldosterone, the effect being more pronounced in proximal rather than distal small intestine [117], In this experiment, however, the intestinal loops were subjected to a preliminary wash with distilled water, a treatment known to severely damage the mucosa.…”

The Effect of Aldosterone on the Electrical Activity of Rat Colon

“…aldosterone. The latter results can be compared with those of Elmslie, Mulholland & Shields (1966) who also found that even a large dose of spironolactone did not block the effects of aldosterone on K+ secretion by dog colon completely. Despite its widespread clinical use as an aldosterone antagonist, spironolactone does therefore appear to be relatively inefficient.…”

Action of aldosterone upon the intestinal transport of potassium, sodium, and water.

“…A similar delay in the effect of aldosterone upon the renal excretion of electrolytes has been described in the dog (Barger et al, 1958) and in man (Dingman, Finkenstaedt, Laidlaw, Renold, Jenkins, Merrill, and Thorn, 1958). Second, the action of aldosterone upon the intestinal transport of electrolytes can be inhibited by spironolactones (Elmslie, Mulholland, and Shields, 1966), which also act upon the kidney as competitive blockers (Bartter, 1960). Third, the marked alterations in urinary electrolyte excretion which follow sodium depletion are accompanied by identical changes in the intestinal handling of electrolytes (Clarke and Shields, 1963).…”