Overexpression of eNOS in brain stem reduces enhanced sympathetic drive in mice with myocardial infarction

Koji Sakai, Yoshitaka Hirooka, Hideaki Shigematsu, Takuya Kishi, Koji Ito, Hiroaki Shimokawa, Akira Takeshita, Kenji Sunagawa

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Abstract

Reduced nitric oxide (NO) in the brain might contribute to enhanced sympathetic drive in heart failure (HF). The aim of this study was to determine whether increased NO production induced by local overexpression of endothelial NO synthase (eNOS) in the nucleus tractus solitarius (NTS) of the brain stem reduces the enhanced sympathetic drive in mice with HF. Myocardial infarction (MI) was induced in mice by ligating the left coronary artery. MI mice exhibited left ventricular dilatation and a reduced left ventricular ejection fraction. Urinary norepinephrine excretion in MI mice was greater than that in sham-operated mice, indicating that sympathetic drive was enhanced in this model. Thus this model has features that are typical of HF. Western blot analysis and immunohistochemical staining for neuronal NOS (nNOS) indicated that nNOS protein expression was significantly reduced in the brain stem of MI mice. MI mice had a significantly smaller increase in blood pressure evoked by intracisternal injection of NG-monomethyl-L-arginine than sham-operated mice. Adenoviral vectors encoding either eNOS (AdeNOS) or β-galactosidase (Adβgal) were transfected into the NTS to examine the effect of increased NO production in the NTS on the enhanced sympathetic drive in HF. After the gene transfer, urinary norepinephrine excretion was reduced in AdeNOS-transfected MI mice but not in Adβgal-transfected MI mice. These results indicate that nNOS expression in the brain stem, especially in the NTS, is reduced in the MI mouse model of HF, and increased NO production induced by overexpression of eNOS in the NTS attenuates the enhanced sympathetic drive in this model.

Original languageEnglish
Pages (from-to)H2159-H2166
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume289
Issue number5 58-5
DOIs
Publication statusPublished - Nov 2005

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Sakai, K., Hirooka, Y., Shigematsu, H., Kishi, T., Ito, K., Shimokawa, H., Takeshita, A., & Sunagawa, K. (2005). Overexpression of eNOS in brain stem reduces enhanced sympathetic drive in mice with myocardial infarction. American Journal of Physiology - Heart and Circulatory Physiology, 289(5 58-5), H2159-H2166. https://doi.org/10.1152/ajpheart.00408.2005