Evidence for a role of vasopressin in the control of aldosterone secretion in primary aldosteronism: in vitro and in vivo studies.
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.[1]References
- Evidence for a role of vasopressin in the control of aldosterone secretion in primary aldosteronism: in vitro and in vivo studies. Perraudin, V., Delarue, C., Lefebvre, H., Do Rego, J.L., Vaudry, H., Kuhn, J.M. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
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