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The Journal of clinical endocrinology and metabolism

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


PMID 16449345

Abstract

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. The objective of the study was to investigate in vitro and in vivo the possible involvement of AVP in the physiopathology of primary aldosteronism. 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. The study was conducted at a university hospital and research laboratory. The study population included eight untreated patients with primary aldosteronism, four with APA and four with idiopathic hyperaldosteronism. Aldosterone secretion of APA cells in vitro and plasma aldosterone, renin, and ACTH were measured. SR 49059 (200 mg once daily) or placebo was administered during two 1-wk treatment periods separated by a 2-wk washout. 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. 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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S5701
SR 49059, ≥97% (HPLC)
C28H27Cl2N3O7S