title: Biphasic time course of the changes in aldosterone biosynthesis under high-salt conditions in Dahl salt-sensitive rats.
abstract: OBJECTIVE
  The comorbidity of excess salt and elevated plasma aldosterone has deleterious effects in cardiovascular disease. We evaluated the mechanisms behind the paradoxical increase in aldosterone biosynthesis in relation to dietary intake of salt.
  
  
  RESULTS
  Dahl salt-sensitive (Dahl-S) and salt-resistant (Dahl-R) rats were fed a high-salt diet, and plasma and tissue levels of aldosterone in the adrenal gland and heart were quantified by liquid chromatography-electrospray ionization-tandem mass spectrometry. In Dahl-S rats, we found that the delayed and paradoxical increase in aldosterone biosynthesis after the initial and appropriate response to high salt. The late rise in aldosterone biosynthesis was accompanied by upregulation of CYP11B2 expression in the zona glomerulosa and increased adrenal angiotensin II levels and renin-angiotensin system components. It preceded the appearance of left ventricular systolic dysfunction and renal insufficiency. Blockade of angiotensin AT(1) receptors reversed the paradoxical increase in aldosterone biosynthesis. In contrast, Dahl-R rats maintained the initial suppression of aldosterone biosynthesis. Aldosterone levels in the heart closely paralleled those in the plasma and adrenal gland and disappeared after bilateral adrenalectomy.
  
  
  CONCLUSIONS
  Chronic salt overload in Dahl-S rats stimulates aberrant aldosterone production via activation of the local renin-angiotensin system in the adrenal gland, thereby creating the comorbidity of excess salt and elevated plasma aldosterone.
authors.affiliation: Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Morizane
authors.forename: Fumiko
authors.initials: F
authors.lastname: Mitani
authors.forename: Kae
authors.initials: K
authors.lastname: Ozawa
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ito
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsuhashi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Katsumata
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ito
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Yan
authors.forename: Ken
authors.initials: K
authors.lastname: Shinmura
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Seijiro
authors.initials: S
authors.lastname: Honma
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: John W
authors.initials: JW
authors.lastname: Funder
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
authors.forename: Motoaki
authors.initials: M
authors.lastname: Sano
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism; D000450:Aldosterone / Q000096:biosynthesis*; D000818:Animals; D004195:Disease Models, Animal; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D012982:Sodium, Dietary / Q000009:adverse effects*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D012982:Sodium, Dietary; D000450:Aldosterone