Effect of Serotonin 4 (5-HT 4 ) Receptor Agonists on Aldosterone Secretion in Idiopathic Hyperaldosteronism

Hervé Lefebvre (1) , Dorthe Cartier (1) , Celine Duparc (1) , Vincent Contesse (1) , Isabelle Lihrmann (1) , Catherine Delarue (1) , Hubert Vaudry (1) , Rodolphe Fischmeister (2) , Jean-Marc Kuhn (1)

1 IFRMP 23 - Institut Fédératif de Recherches Multidisciplinaires sur les Peptides
2 CARPAT (UMRS1180) - Signalisation et physiopathologie cardiovasculaire

Serotonin (5-HT) stimulates aldosterone secretion in man through 5-HT4 receptors positively coupled to adenylyl cyclase. In particular, it has been shown that oral administration of a single dose of the 5-HT4 receptor agonist cisapride induces a significant increase in plasma aldosterone levels (PAL) in healthy volunteers. Idiopathic hyperaldosteronism (IH) is a rare disorder characterized by hypertension, hypokalemia and bilateral adrenal hypersecretion of aldosterone. In patients with IH, administration of the 5-HT precursor 5-hydroxytryptophan (5-HTP) is followed by a significant increase in PAL. 5-HTP-induced aldosterone secretion has been attributed to the activation of central serotonergic pathways, The aim of the present study was to evaluate the effect of the oral administration of a single dose of cisapride (1 0 mg) on aldosterone secretion in IS patients with IH, in a simple blind fashion versus placebo. Cisapride induced a significant increase in PAL but did not affect renin, cortisol and potassium levels. The present study demonstrates that 5-HT4 receptor agonists are able to stimulate aldosterone secretion in patients with IH. These data also indicate that hyperplastic glomerulosa tissue, like normal glomerulosa cells, expresses a functional 5-HT4 receptor. Therefore, 5-HT4 receptor antagonists may represent a new approach in the treatment of primary hyperaldosteronism.

Mots clés: serotonin; 5-HT 4 receptor; aldosterone; Conn's adenoma; cisapride; GR 113808

Domaines: Endocrinologie et métabolisme

Hervé Lefebvre, Dorthe Cartier, Celine Duparc, Vincent Contesse, Isabelle Lihrmann, et al.. Effect of Serotonin 4 (5-HT 4 ) Receptor Agonists on Aldosterone Secretion in Idiopathic Hyperaldosteronism. Endocrine Research, 2000, 26 (4), pp.583-587. ⟨10.3109/07435800009048575⟩. ⟨hal-03611671⟩