Evidence for a role of vasopressin in the control of aldosterone secretion in primary aldosteronism: in vitro and in vivo studies.
J Clin Endocrinol Metab
; 91(4): 1566-72, 2006 Apr.
Article
em En
| MEDLINE
| ID: mdl-16449345
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 OUTCOMEMEASURES:
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasopressinas
/
Aldosterona
/
Hiperaldosteronismo
Tipo de estudo:
Clinical_trials
Limite:
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article