Aldosterone-induced organ damage: plasma aldosterone level and inappropriate salt status.
In recent years, it has been clarified that aldosterone can directly damage various organs, such as the heart, blood vessel, and kidneys, via non-epithelial mineralocorticoid receptors, independent of changes in blood pressure. Anti-aldosterone drugs have been clinically reported to be useful for their organ-protecting effects. The fact that these effects have been considered important for almost 10 years seems to indicate that aldosterone-induced organ damage can develop as a consequence of plasma aldosterone levels being in disproportion to salt status. In a previous study, cardiac fibrosis could not be induced in an experimental model of hyperaldosteronism with a low-salt diet. It is, therefore, extremely important to understand the relationship between plasma aldosterone level and inappropriate salt balance when considering diseases or states for which an anti-aldosterone drug is called for. In this paper we review the fundamental and clinical studies reported to date, mainly to investigate the pathology of organ damage induced by aldosterone and excess salt. Aldosterone-induced direct organ damage mediated through vasculitis essentially requires salt, which is inappropriate for plasma aldosterone level, and studies performed from this standpoint may provide a clue to the clarification of the involvement of salt in the actions of aldosterone via non-epithelial mineralocorticoid receptors. In humans, it is also strongly suggested that organ damage may occur, even at a plasma aldosterone level within a normal range, if salt intake is imbalanced to the aldosterone level. This means that the new aldosterone blocker eplerenone may also have significance as a drug inhibiting inflammation, possibly serving as a trigger of organ damage.
Sato
Atsuhisa
A
Department of Internal Medicine, Mito Red Cross Hospital, San-no-maru, Mito, Japan. atsu-sa@pb3.so-net.ne.jp
Saruta
Takao
T
D000450:Aldosterone / Q000097:blood*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology* / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D012084:Renin-Angiotensin System; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D014657:Vasculitis / Q000209:etiology*
D018161:Receptors, Mineralocorticoid; D017673:Sodium Chloride, Dietary; D017923:Sodium-Hydrogen Exchangers; D000804:Angiotensin II; D000450:Aldosterone