THE SEROTONIN-4 RECEPTOR AGONIST CISAPRIDE AND ANGIOTENSIN-II EXERT ADDITIVE EFFECTS ON ALDOSTERONE SECRETION IN NORMAL MAN

In animals and man, serotonin (5-HT) exerts a direct stimulatory actio n on adrenocortical cells through activation of 5-HT, receptors. In ra ts, 5-HT also potentiates the stimulatory effect of angiotensin-II (An g II) on aldosterone secretion. The aim of the present study was to in vestigate the effect of concomitant administration of the 5-HT4 recept or agonist, cisapride, and Ang II on aldosterone secretion in normal h uman subjects. Eight healthy male volunteers pretreated with dexametha sone received, at 1-week intervals in random order and simple blind fa shion, the following treatments: 1) a single oral dose of 10 mg cisapr ide, 2) a single oral dose of placebo, 3) a perfusion of graded doses of Ang II (from 1-4 ng/kg.min), 4) a perfusion of placebo, and 5) a si ngle oral dose of 10 mg cisapride associated with a perfusion of Ang I I. The oral doses of cisapride and placebo were also administered afte r a S-day period of a low sodium diet (10 mmol/day). Plasma aldosteron e levels increased significantly within 90 min after the administratio n of cisapride without any change in renin levels. The comparison betw een the net increase in aldosterone production induced by cisapride, A ng II, and cisapride plus Ang II showed that the stimulatory effects o f cisapride and Ang II on aldosterone secretion were only additive. Si milarly, the increase in plasma aldosterone levels induced by a sodium -restricted diet was just additive with the cisapride-evoked stimulati on of aldosterone secretion. These results provide further evidence th at the action of 5-HT on glomerulosa cells is mediated through activat ion of 5-HT4 receptors. The data also indicate that in humans, 5-HT do es not potentiate the stimulatory effect of Ang IT on aldosterone secr etion.