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Heart and Vessels
Erschienen in: Heart and Vessels 5/2013

01.09.2013 | Original Article

Atrial natriuretic peptide exerts protective action against angiotensin II-induced cardiac remodeling by attenuating inflammation via endothelin-1/endothelin receptor A cascade

verfasst von: 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

Erschienen in: Heart and Vessels | Ausgabe 5/2013

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Abstract

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.
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Metadaten
Titel
Atrial natriuretic peptide exerts protective action against angiotensin II-induced cardiac remodeling by attenuating inflammation via endothelin-1/endothelin receptor A cascade
verfasst von
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
Publikationsdatum
01.09.2013
Verlag
Springer Japan
Erschienen in
Heart and Vessels / Ausgabe 5/2013
Print ISSN: 0910-8327
Elektronische ISSN: 1615-2573
DOI
https://doi.org/10.1007/s00380-012-0311-0

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