Nitrosonifedipine, a photodegradation product of nifedipine, suppresses pharmacologically induced aortic aneurysm formation

Masaki Imanishi, Yuki Izawa-Ishizawa, Takumi Sakurada, Yusuke Kohara, Yuya Horinouchi, Eriko Sairyo, Yoshito Zamami, Kenshi Takechi, Masayuki Chuma, Keijo Fukushima, Yasumasa Ikeda, Hiromichi Fujino, Masanori Yoshizumi, Koichiro Tsuchiya, Toshiaki Tamaki, Keisuke Ishizawa

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Background/Aims: We have reported that nitrosonifedipine (NO-NIF), a photodegradation product of nifedipine, has strong antioxidant and endothelial protective effects, and can suppress several cardiovascular diseases in animal models. The objective of the present study was to investigate the effects of NO-NIF on aortic aneurysm formation. Methods: The mice were infused with β-aminopropionitrile for 2 weeks and angiotensin II for 6 weeks to induce aortic aneurysm formation. The oxidative stress was measured by dihydroethidium staining and nitrotyrosine staining. The expressions of inflammation-related genes were assessed by quantitative real-time PCR and immunohistochemical staining. To clarify the mechanisms of how NO-NIF suppresses vascular cell adhesion molecule (VCAM)-1, endothelial cells were used in in vitro system. Results: NO-NIF suppressed pharmacologically induced the aortic aneurysm formation and aortic expansion without blood pressure changes. NO-NIF suppressed elastin degradation and matrix metalloproteinase-2 mRNA expression. NO-NIF suppressed the reactive oxygen species-cyclophilin A positive feedback loop. Upregulated mRNA expressions of inflammation-related genes and endothelial VCAM-1 were suppressed by NO-NIF co-treatment in aortae. Conclusion: NO-NIF has the potential to be a new, nifedipine-derived therapeutic drug for suppressing aortic aneurysm formation by directly improving aortic structure with its strong ability to reduce oxidative stress and inflammation.

Original languageEnglish
Pages (from-to)281-286
Number of pages6
JournalPharmacology
Volume102
Issue number5-6
DOIs
Publication statusPublished - Nov 1 2018
Externally publishedYes

Keywords

  • Aorta
  • Aortic aneurysm
  • Nitrosonifedipine
  • Oxidative stress

ASJC Scopus subject areas

  • Pharmacology

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