Evidence for a role of vasopressin in the control of aldosterone secretion in primary aldosteronism: in vitro and in vivo studies.
BACKGROUND
Arginine vasopressin (AVP) stimulates steroid secretion from the normal human adrenal gland and some cortisol-producing adrenocortical tumors or hyperplasia through activation of the V(1a) receptor.


OBJECTIVE
The objective of the study was to investigate in vitro and in vivo the possible involvement of AVP in the physiopathology of primary aldosteronism.


METHODS
The design of the study included immunohistochemical, pharmacological, and molecular studies on aldosterone-producing adenoma (APA), followed by a monocentric, crossover trial of the orally active V(1a) receptor antagonist, SR 49059, in a double blind, randomized, and placebo-controlled fashion.


METHODS
The study was conducted at a university hospital and research laboratory.


METHODS
The study population included eight untreated patients with primary aldosteronism, four with APA and four with idiopathic hyperaldosteronism.


METHODS
Aldosterone secretion of APA cells in vitro and plasma aldosterone, renin, and ACTH were measured.


METHODS
SR 49059 (200 mg once daily) or placebo was administered during two 1-wk treatment periods separated by a 2-wk washout.


RESULTS
We observed the occurrence of AVP-containing cells in APA tissues. Administration of AVP to perifused APA cells induced an increase in aldosterone production, which was inhibited by a specific V(1a) antagonist. RT-PCR analysis showed the expression of V(1a) receptor mRNA in most APAs studied. In APA patients, SR 49059 did not induce any effect on basal aldosterone secretion but provoked a plasma aldosterone response to orthostatism (P < 0.03) and strengthened the positive correlation between plasma aldosterone and ACTH.


CONCLUSIONS
The present study indicates that functional V(1a) receptors are present in APA and suggests that AVP may exert an autocrine/paracrine control of aldosterone secretion in APA tissues.
Perraudin
Véronique
V
INSERM Unité 413, Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide Research (Institut Fédératif de Recherche Multidisciplinaires sur les Peptides 23), University of Rouen, 76821 Mont-Saint-Aignan, France.
Delarue
Catherine
C
Lefebvre
Hervé
H
Do Rego
Jean-Luc
JL
Vaudry
Hubert
H
Kuhn
Jean-Marc
JM
D000236:Adenoma / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000450:Aldosterone / Q000096:biosynthesis / Q000378:metabolism*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005455:Fluorescent Antibody Technique; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D006929:Hyperaldosteronism / Q000378:metabolism*; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D017483:Receptors, Vasopressin / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014667:Vasopressins / Q000502:physiology*
D006727:Hormone Antagonists; D007211:Indoles; D011759:Pyrrolidines; D017483:Receptors, Vasopressin; D014667:Vasopressins; D000450:Aldosterone; D012313:RNA; D000324:Adrenocorticotropic Hormone; C082134:relcovaptan