| Project/Area Number |
22790721
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Nara Medical University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| 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 |
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| 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.
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