The role of GC-A signaling against aldosterone and salt-induced cardiac remodeling

2011 Fiscal Year Final Research Report

• Project/Area Number: 22790721
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Nara Medical University
• Principal Investigator: SOMEKAWA Satoshi 奈良県立医科大学, 医学部, 講師 (90453167)
• Project Period (FY): 2010 – 2011
• Keywords: グアニリルシクラーゼ / ナトリウム利尿ペプチド / 食塩 / アルドステロン

Research Abstract

Aldosterone(ALD) participates in hypertension and cardiac remodeling through mineralocorticoid receptor(MR). Natriuretic peptide(ANP and BNP) and guanylyl cyclase-A/natriuretic peptide receptor(GC-A) signaling attenuates MR-signaling induced cardiac remodeling. However, the relationship of GC-A signaling and salt toxicity on ALD-induced cardiac remodeling is not fully understood. We investigated whether GC-A interacts with salt effect on ALD-induced cardiac remodeling(hypertrophy and fibrosis) with various dietary salt conditions in wild type mice(WT) and GC-A-KO. Male 12-weeks old WT and GC-A-KO were assigned to control and ALD-treatment group with low dietary salt(LS)(0.001% NaCl), normal dietary salt(NS)(0.6% NaCl) and high dietary salt(HS)(6.0% NaCl). Subpressor dose of exogenous ALD(100ng/kg/min) for 4 weeks significantly exacerbated cardiac remodeling in GC-A KO with NS and HS but not in GC-A KO with LS, and WT with any dietary salt conditions. ALD did not change blood pressure(BP) in either WT or GC-A-KO in any salt conditions. There were no significant difference in MR localization and MR mRNA levels between WT and GC-A KO in each salt condition. The degree of ALD-induced cardiac remodeling in GC-A KO with HS was significantly higher than in GC-A KO with NS, in association with higher expression levels of Nox4 mRNA and oxidative stress. These data may indicated that GC-A signaling interact MR-induced cardiac remodeling in BP-independent but salt toxicity-oxidative stress dependent manner.

Research Products

• [Presentation] GC-A Signaling Attenuates Salt Toxicity on Aldosterone-Induced Cardiac Remodeling (2010)
  • Author(s): Somekawa S, Hitoshi N, Matsumoto T, Sung J H, Nishida T, Soeda T, Takemoto Y, Onoue K, Okayama S, Ishigami K, Takeda Y, Kawata H, Horii M, Uemura S, Saito Y
  • Organizer: International Symposium on Cardiovascular Endocrinology and Metabolism(CVEM)
  • Place of Presentation: Nara, Japan
  • Year and Date: 20100000