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.