Evidence for a role of vasopressin in the control of aldosterone secretion in primary aldosteronism: in vitro and in vivo studies.

Abstract

CONTEXT:

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.

DESIGN:

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.

SETTING:

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

PATIENTS:

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

MAIN OUTCOME MEASURES:

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

INTERVENTION:

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.

• Authors: Véronique Perraudin, Catherine Delarue, Hervé Lefebvre, Jean-Luc Do Rego, Hubert Vaudry, Jean-Marc Kuhn
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 91 Issue 4 Pg. 1566-72 (Apr 2006) ISSN: 0021-972X [Print] United States
• PMID: 16449345 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Hormone Antagonists
• Indoles
• Pyrrolidines
• Receptors, Vasopressin
• Vasopressins
• Aldosterone
• RNA
• Adrenocorticotropic Hormone
• relcovaptan

Topics

• Adenoma (metabolism)
• Adrenocorticotropic Hormone (blood)
• Aldosterone (biosynthesis, metabolism)
• Cross-Over Studies
• Double-Blind Method
• Female
• Fluorescent Antibody Technique
• Hormone Antagonists (pharmacology)
• Humans
• Hyperaldosteronism (metabolism)
• Immunohistochemistry
• Indoles (pharmacology)
• Male
• Middle Aged
• Pituitary Neoplasms (metabolism)
• Pyrrolidines (pharmacology)
• RNA (biosynthesis, genetics)
• Receptors, Vasopressin (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Vasopressins (physiology)