EPA effect on NOS gene expression and on NO level in endothelin-1-induced hypertrophied cardiomyocytes

Nobutake Shimojo, Subrina Jesmin, Sohel Zaedi, Masaaki Soma, Tsutomu Kobayashi, Seiji Maeda, Iwao Yamaguchi, Katsutoshi Goto, Takashi Miyauchi

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Cardiomyocytes release (or metabolize) several diffusible agents (e.g., nitric oxide [NO], endothelin-1 [ET-1], and angiotensin II) that exert direct effects on myocyte function under various pathologic conditions. Although cardiac hypertrophy is a compensatory mechanism in response to different cardiovascular diseases, there can be a pathologic transition in which the myocardium becomes dysfunctional. Recently, NO has been found to be an important regulator of cardiac remodeling. Specifically, NO has been recognized as a potent antihypertrophic and proapoptotic mediator in cultured cardiomyocytes. We demonstrated that ET-1-induced hypertrophic remodeling in neonatal cardiomyocytes was arrested by pretreatment with eicosapentaenoic acid (EPA), a major component of fish oil. In some recent studies, EPA has demonstrated cardioprotective effects by modulating NO. This study investigated the changes in NO synthase (NOS) in ET-1-induced hypertrophied cardiomyocytes and in total levels of nitrates and nitrites. Ventricular cardiomyocytes were isolated from 2-day-old Sprague-Dawley rats and were cultured in D-MEM/Ham F12 supplemented with 0.1% fatty acid-free bovine serum albumin for 3 days. At Day 4 of culture, the cardiomyocytes were divided into three groups: control group, ET-1 (0.1 nM) group, and ET-1 pretreated with EPA (10 μM) group. NOS gene expression was evaluated 24 hrs after treatment using real-time polymerase chain reaction. Endothelial NOS (eNOS) mRNA expression was decreased in the ET-1 group compared with controls and was unchanged by pretreatment with EPA. mRNA expression of inducible NOS (iNOS) was significantly increased in ET-1-treated cardiomyocytes and was suppressed by EPA pretreatment. Neuronal NOS gene expression and total NO level did not exhibit a statistically significant change in any of the groups. There may be some interaction between ET-1, eNOS, and iNOS in ET-1-induced and EPA-regressed hypertrophied cardiomyocytes that suppress iNOS expression without modulating total NO level or eNOS gene expression.

Original languageEnglish
Pages (from-to)913-918
Number of pages6
JournalExperimental Biology and Medicine
Volume231
Issue number6
Publication statusPublished - 2006 Jun
Externally publishedYes

Keywords

  • Eicosapentaenoic acid (EPA)
  • Endothelin-1
  • Hypertrophy
  • Neonatal cardiomyocytes
  • Nitric oxide and nitric oxide synthase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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