title: Salt accelerates aldosterone-induced cardiac remodeling in the absence of guanylyl cyclase-A signaling.
abstract: OBJECTIVE
  Excess sodium causes the development of cardiovascular diseases in conjunction with enhancing renin-angiotensin-aldosterone system (RAAS). Natriuretic peptides are sodium regulators and prevent pathological cardiac alterations by counteracting RAAS. However, it is unknown whether natriuretic peptides inhibit the sodium effect in adverse cardiac alterations. Here, we investigated whether excess salt intake could exacerbate cardiac remodeling in mice with impaired natriuretic peptide signaling.
  
  
  METHODS
  Mice lacking the gene encoding the natriuretic peptide receptor, guanylyl cyclase-A (GC-A), and wild-type mice were administered with either a vehicle substance or a subpressor dose of aldosterone (100ng/kg/min), alongside low salt (0.001% NaCl), normal salt (0.6% NaCl), or high salt diets (6.0% NaCl) for four weeks. Mice were then sacrificed and the hearts were evaluated by histology and RT-PCR.
  
  
  RESULTS
  Salt load did not induce cardiac changes in vehicle and aldosterone groups in wild-type mice. On the other hand, cardiac hypertrophy and interstitial fibrosis were significantly exacerbated in a salt dependent manner in GC-A knockout (KO) mice administered aldosterone, and were associated with enhanced gene expression relevant to hypertrophy, fibrosis, and oxidative stress conditions. Of note, excess salt intake increased the expression of Sgk1, serum and glucocorticoid responsive kinase-1, in aldosterone-administered GC-A KO mice. These molecular changes were not observed in wild-type mice.
  
  
  CONCLUSIONS
  The results of the present study demonstrate that excess salt intake induced cardiac remodeling in conjunction with aldosterone administration in GC-A KO mice, indicating that GC-A signaling attenuated the deleterious salt effect in aldosterone-induced cardiac remodeling.
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakagawa
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Somekawa
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Onoue
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kumazawa
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Ueda
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Seno
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Nakada
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nakano
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Matsui
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Tunenari
authors.initials: T
authors.lastname: Soeda
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okayama
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Kawakami
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawata
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Okura
authors.affiliation: First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan. Electronic address: yssaito@naramed-u.ac.jp.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Saito
mesh_terms: D000450:Aldosterone / Q000008:administration & dosage*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012965:Sodium Chloride / Q000494:pharmacology*
chemical_list: D012965:Sodium Chloride; D000450:Aldosterone
keywords: Aldosterone; Cardiac remodeling; Mineralocorticoid receptor; Natriuretic peptide; Salt intake