Chronic C-Type Natriuretic Peptide Infusion Attenuates Angiotensin II-Induced Myocardial Superoxide Production and Cardiac Remodeling
Myocardial oxidative stress and inflammation are key mechanisms in cardiovascular remodeling. C-type natriuretic peptide (CNP) is an endothelium-derived cardioprotective factor, although its effect on cardiac superoxide generation has not been investigated in vivo. This study tested the hypothesis t...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2012-01-01
|
| Series: | International Journal of Vascular Medicine |
| Online Access: | http://dx.doi.org/10.1155/2012/246058 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832556298061742080 |
|---|---|
| author | Yasuhiro Izumiya Satoshi Araki Hiroki Usuku Taku Rokutanda Shinsuke Hanatani Hisao Ogawa |
| author_facet | Yasuhiro Izumiya Satoshi Araki Hiroki Usuku Taku Rokutanda Shinsuke Hanatani Hisao Ogawa |
| author_sort | Yasuhiro Izumiya |
| collection | DOAJ |
| description | Myocardial oxidative stress and inflammation are key mechanisms in cardiovascular remodeling. C-type natriuretic peptide (CNP) is an endothelium-derived cardioprotective factor, although its effect on cardiac superoxide generation has not been investigated in vivo. This study tested the hypothesis that suppression of superoxide production contributes to the cardioprotective action of CNP. Angiotensin II (Ang II) or saline was continuously infused subcutaneously into mice using an osmotic minipump. Simultaneously with the initiation of Ang II treatment, mice were infused with CNP (0.05 μg/kg/min) or vehicle for 2 weeks. The heart weight to tibial length ratio was significantly increased by Ang II in vehicle-treated mice. Treatment with CNP decreased Ang II-induced cardiac hypertrophy without affecting systolic blood pressure. Echocardiography showed that CNP attenuated Ang II-induced increase in wall thickness, left ventricular dilatation, and decrease in fractional shortening. CNP reduced Ang II-induced increases in cardiomyocyte size and interstitial fibrosis and suppressed hypertrophic- and fibrosis-related gene expression. Finally, CNP decreased Ang II-induced cardiac superoxide production. These changes were accompanied by suppression of NOX4 gene expression. Our data indicate that treatment with CNP attenuated Ang II-induced cardiac hypertrophy, fibrosis, and contractile dysfunction which were accompanied by reduced cardiac superoxide production. |
| format | Article |
| id | doaj-art-cc4d7cb66baa4ad5b6c6e01f59a15afc |
| institution | Kabale University |
| issn | 2090-2824 2090-2832 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Vascular Medicine |
| spelling | doaj-art-cc4d7cb66baa4ad5b6c6e01f59a15afc2025-02-03T05:45:47ZengWileyInternational Journal of Vascular Medicine2090-28242090-28322012-01-01201210.1155/2012/246058246058Chronic C-Type Natriuretic Peptide Infusion Attenuates Angiotensin II-Induced Myocardial Superoxide Production and Cardiac RemodelingYasuhiro Izumiya0Satoshi Araki1Hiroki Usuku2Taku Rokutanda3Shinsuke Hanatani4Hisao Ogawa5Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, JapanDepartment of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, JapanDepartment of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, JapanDepartment of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, JapanDepartment of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, JapanDepartment of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, JapanMyocardial oxidative stress and inflammation are key mechanisms in cardiovascular remodeling. C-type natriuretic peptide (CNP) is an endothelium-derived cardioprotective factor, although its effect on cardiac superoxide generation has not been investigated in vivo. This study tested the hypothesis that suppression of superoxide production contributes to the cardioprotective action of CNP. Angiotensin II (Ang II) or saline was continuously infused subcutaneously into mice using an osmotic minipump. Simultaneously with the initiation of Ang II treatment, mice were infused with CNP (0.05 μg/kg/min) or vehicle for 2 weeks. The heart weight to tibial length ratio was significantly increased by Ang II in vehicle-treated mice. Treatment with CNP decreased Ang II-induced cardiac hypertrophy without affecting systolic blood pressure. Echocardiography showed that CNP attenuated Ang II-induced increase in wall thickness, left ventricular dilatation, and decrease in fractional shortening. CNP reduced Ang II-induced increases in cardiomyocyte size and interstitial fibrosis and suppressed hypertrophic- and fibrosis-related gene expression. Finally, CNP decreased Ang II-induced cardiac superoxide production. These changes were accompanied by suppression of NOX4 gene expression. Our data indicate that treatment with CNP attenuated Ang II-induced cardiac hypertrophy, fibrosis, and contractile dysfunction which were accompanied by reduced cardiac superoxide production.http://dx.doi.org/10.1155/2012/246058 |
| spellingShingle | Yasuhiro Izumiya Satoshi Araki Hiroki Usuku Taku Rokutanda Shinsuke Hanatani Hisao Ogawa Chronic C-Type Natriuretic Peptide Infusion Attenuates Angiotensin II-Induced Myocardial Superoxide Production and Cardiac Remodeling International Journal of Vascular Medicine |
| title | Chronic C-Type Natriuretic Peptide Infusion Attenuates Angiotensin II-Induced Myocardial Superoxide Production and Cardiac Remodeling |
| title_full | Chronic C-Type Natriuretic Peptide Infusion Attenuates Angiotensin II-Induced Myocardial Superoxide Production and Cardiac Remodeling |
| title_fullStr | Chronic C-Type Natriuretic Peptide Infusion Attenuates Angiotensin II-Induced Myocardial Superoxide Production and Cardiac Remodeling |
| title_full_unstemmed | Chronic C-Type Natriuretic Peptide Infusion Attenuates Angiotensin II-Induced Myocardial Superoxide Production and Cardiac Remodeling |
| title_short | Chronic C-Type Natriuretic Peptide Infusion Attenuates Angiotensin II-Induced Myocardial Superoxide Production and Cardiac Remodeling |
| title_sort | chronic c type natriuretic peptide infusion attenuates angiotensin ii induced myocardial superoxide production and cardiac remodeling |
| url | http://dx.doi.org/10.1155/2012/246058 |
| work_keys_str_mv | AT yasuhiroizumiya chronicctypenatriureticpeptideinfusionattenuatesangiotensiniiinducedmyocardialsuperoxideproductionandcardiacremodeling AT satoshiaraki chronicctypenatriureticpeptideinfusionattenuatesangiotensiniiinducedmyocardialsuperoxideproductionandcardiacremodeling AT hirokiusuku chronicctypenatriureticpeptideinfusionattenuatesangiotensiniiinducedmyocardialsuperoxideproductionandcardiacremodeling AT takurokutanda chronicctypenatriureticpeptideinfusionattenuatesangiotensiniiinducedmyocardialsuperoxideproductionandcardiacremodeling AT shinsukehanatani chronicctypenatriureticpeptideinfusionattenuatesangiotensiniiinducedmyocardialsuperoxideproductionandcardiacremodeling AT hisaoogawa chronicctypenatriureticpeptideinfusionattenuatesangiotensiniiinducedmyocardialsuperoxideproductionandcardiacremodeling |