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Cardiovascular Research 1998 38(1):192-197; doi:10.1016/S0008-6363(97)00317-9
© 1998 by European Society of Cardiology
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Copyright © 1998, European Society of Cardiology

Effects of vesnarinone on nitric oxide synthesis in rat cardiac myocytes

Kenji Kurosaki, Uichi Ikeda*, Yoshikazu Maeda, Masahisa Shimpo, Shuichi Ueno and Kazuyuki Shimada

Department of Cardiology, Jichi Medical School, Minamikawachi-machi, Tochigi 329-04, Japan

* Corresponding author. Tel.: +81 (285) 442111 ext. 3556; fax: +81 (285) 445317; e-mail: uikeda@jichi.ac.jp

Objective: The purpose of this study was to investigate the effects of vesnarinone on nitric oxide (NO) synthesis in cardiac myocytes. Methods: We measured the accumulation of nitrite, a stable oxidation product of NO, and the expression of inducible NO synthase (iNOS) protein in cultured neonatal rat cardiac myocytes. Results: Incubation of the cultures with interleukin-1β (IL-1β; 10 ng/ml) and tumor necrosis factor {alpha} (TNF{alpha}; 10 ng/ml) caused a marked increase in nitrite production. Although vesnarinone by itself showed no effect on nitrite accumulation, it enhanced cytokine-induced nitrite production by cardiac myocytes in a dose-dependent manner. The effect of vesnarinone was completely abolished in the presence of NG-monomethyl-L-arginine or actinomycin D. The vesnarinone-induced nitrite production was accompanied by increased iNOS protein expression. In the presence of dibutyryl-cAMP, cytokine-induced nitrite accumulation was further increased, but the stimulatory effect of vesnarinone on nitrite accumulation was diminished. The effect of vesnarinone was also inhibited by Rp-8-Br-cAMPS, a competitive inhibitor of protein kinase A, in a dose-dependent manner. Conclusions: These findings indicate that vesnarinone increases NO synthesis in cytokine-stimulated cardiac myocytes, at least partially through a cAMP-dependent pathway.

KEYWORDS Vesnarinone; Nitric oxide; Cardiac myocyte; Myocyte; Cytokine


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