Roles of bone morphogenetic protein-6 in aldosterone regulation by adrenocortical cells.
Aldosterone production occurs in the adrenal cortex, and is regulated primarily by angiotensin II (Ang II), potassium and adrenocorticotropin (ACTH). In the presence of the aldosterone stimulators, steroidogenesis is further governed by local autocrine and/or paracrine factors in the adrenal cortex. We reported the presence of functional bone morphogenetic protein (BMP) system in the adrenal cortex and also demonstrated that BMP-6 increases Ang II-induced aldosterone production, which could be involved in the "aldosterone breakthrough" phenomenon. Aldosterone breakthrough is the phenomenon by which circulating aldosterone concentrations increase above pre-treatment levels after long-term therapy with ACE inhibitors or Ang II type 1 receptor antagonists (ARB). This phenomenon may lead to important clinical consequences since increased aldosterone in a high-salt state facilitates cardiovascular and renal damage in hypertensive patients. We found that long-term ARB treatment reverses the reduction of aldosterone synthesis by adrenocortical cells, thereby causing "cellular aldosterone breakthrough". The availability of BMP-6 in the adrenal cortex may be at least partly involved in the occurrence of cellular escape from aldosterone suppression under chronic treatment with ARB.
Otani
Hiroyuki
H
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Detistry and Pharmaceucial Sciences, Okayama 700-8558, Japan.
Otsuka
Fumio
F
Inagaki
Kenichi
K
Suzuki
Jiro
J
Makino
Hirofumi
H
D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D055418:Bone Morphogenetic Protein 6 / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy
D047228:Angiotensin II Type 1 Receptor Blockers; D055418:Bone Morphogenetic Protein 6; D000450:Aldosterone