Reduced Nitric Oxide Synthase in the Brainstem Contributes to Enhanced Sympathetic Drive in Rats with Heart Failure

Yoshitaka Hirooka, Hideaki Shigematsu, Takuya Kishi, Yoshikuni Kimura, Yoichi Ueta, Akira Takeshita

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)


Recent studies have suggested that central nervous mechanisms are involved in the enhanced sympathetic drive observed in heart failure (HF). Nitric oxide (NO) in the brainstem has been shown to reduce sympathetic nerve activity. The aim of this study was to determine whether the expression of neuronal nitric oxide synthase (nNOS) in the brainstem is reduced in rats with HF. Heart failure was produced by myocardial infarction in Wistar-Kyoto rats (HF group). Hemodynamic and echocardiographic examinations were performed. Western blot analysis for nNOS in the nucleus tractus solitarii (NTS) and the rostral ventrolateral medulla (RVLM) in the brainstem were performed to determine the expression of the nNOS gene in the HF group or sham-operated (control) group. We also performed in situ hybridization for nNOS mRNA and distribution in the brainstem. The expression of nNOS protein in the NTS and the RVLM were reduced in the HF group compared to the control group. The expression of nNOS mRNA in the brainstem was also reduced in the HF group, particularly in the NTS, compared to the control group. Intracistemal injection of N G-monomethyl-L-arginine elicited a smaller pressor response in the HF group than in the control group. These results suggest that reduced nNOS expression in the NTS and the RVLM, and the resulting reduced NO production of these sites, contribute to the enhanced sympathetic drive in HF.

Original languageEnglish
Pages (from-to)S111-S115
JournalJournal of Cardiovascular Pharmacology
Issue numberSUPPL. 1
Publication statusPublished - Dec 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Reduced Nitric Oxide Synthase in the Brainstem Contributes to Enhanced Sympathetic Drive in Rats with Heart Failure'. Together they form a unique fingerprint.

Cite this