Effect of prolonged administration of the serotonin4 (5-HT4) receptor agonist cisapride on aldosterone secretion in healthy volunteers

In man, serotonin (5-HT) has been shown to stimulate aldosterone secretion through activation of 5-HT4 receptors, In particular, we have observed that oral administration of a single dose of the 5-HT4 receptor agonist cisapri de (10 mg) induces a 5-fold increase in plasma aldosterone levels in health y volunteers. Surprisingly, the usual disorders associated with hyperaldost eronism, i.e. hypertension and hypokalemia, have never been reported during chronic treatment with cisapride. In the present study, we have investigat ed the effect of prolonged oral administration of cisapride (10 mg, 3 times /day during 7 days) on aldosterone secretion in 12 healthy volunteers, in a simple blind fashion versus placebo. On day I of the treatment, cisapride induced a significant increase in plasma aldosterone levels (PAL) which ret urned to the values observed after placebo treatment within 10 hrs. On days 2 and 3, PAL were similar in cisapride- and placebo-treated subjects. Urin ary aldosterone, kalemia and reninemia were not influenced by cisapride dur ing the 7 days of the treatment. The present study shows that cisapride onl y exerts a transient stimulatory effect on aldosterone secretion in healthy volunteers. These data explain why long-term. administration of 5-HT4 agon ists does not affect blood pressure in man. They also indicate that prolong ed stimulation of adrenal 5-HT4 receptors in vivo yields to a rapid desensi tization phenomenon, as previously observed in vitro.