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Atrial natriuretic peptide exerts protective action against angiotensin II-induced cardiac remodeling by attenuating inflammation via endothelin-1/endothelin receptor A cascade.
MedLine Citation:
PMID:  23277455     Owner:  NLM     Status:  Publisher    
We aimed to investigate whether atrial natriuretic peptide (ANP) attenuates angiotensin II (Ang II)-induced myocardial remodeling and to clarify the possible molecular mechanisms involved. Thirty-five 8-week-old male Wistar-Kyoto rats were divided into control, Ang II, Ang II + ANP, and ANP groups. The Ang II and Ang II + ANP rats received 1 μg/kg/min Ang II for 14 days. The Ang II + ANP and ANP rats also received 0.1 μg/kg/min ANP intravenously. The Ang II and Ang II + ANP rats showed comparable blood pressure. Left ventricular fractional shortening and ejection fraction were lower in the Ang II rats than in controls; these indices were higher (P < 0.001) in the Ang II + ANP rats than in the Ang II rats. In the Ang II rats, the peak velocity of mitral early inflow and its ratio to atrial contraction-related peak flow velocity were lower, and the deceleration time of mitral early inflow was significantly prolonged; these changes were decreased by ANP. Percent fibrosis was higher (P < 0.001) and average myocyte diameters greater (P < 0.01) in the Ang II rats than in controls. ANP decreased both myocardial fibrosis (P < 0.01) and myocyte hypertrophy (P < 0.01). Macrophage infiltration, expression of mRNA levels of collagen types I and III, monocyte chemotactic protein-1, and a profibrotic/proinflammatory molecule, tenascin-C (TN-C) were increased in the Ang II rats; ANP significantly decreased these changes. In vitro, Ang II increased expression of TN-C and endothelin-1 (ET-1) in cardiac fibroblasts, which were reduced by ANP. ET-1 upregulated TN-C expression via endothelin type A receptor. These results suggest that ANP may protect the heart from Ang II-induced remodeling by attenuating inflammation, at least partly through endothelin 1/endothelin receptor A cascade.
Shuichi Fujita; Naoshi Shimojo; Fumio Terasaki; Kaoru Otsuka; Noriko Hosotani; Yuka Kohda; Takao Tanaka; Tomohiro Nishioka; Toshimichi Yoshida; Michiaki Hiroe; Yasushi Kitaura; Nobukazu Ishizaka; Kyoko Imanaka-Yoshida
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-1
Journal Detail:
Title:  Heart and vessels     Volume:  -     ISSN:  1615-2573     ISO Abbreviation:  Heart Vessels     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8511258     Medline TA:  Heart Vessels     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Cardiology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan.
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