Effects of neuronal norepinephrine uptake blockade on baroreflex neural and peripheral arc transfer characteristics

Toru Kawada, Tadayoshi Miyamoto, Kazunori Uemura, Koji Kashihara, Atsunori Kamiya, Masaru Sugimachi, Kenji Sunagawa

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Neuronal uptake is the most important mechanism by which norepinephrine (NE) is removed from the synaptic clefts at sympathetic nerve terminals. We examined the effects of neuronal NE uptake blockade on the dynamic sympathetic regulation of the arterial baroreflex because dynamic characteristics are important for understanding the system behavior in response to exogenous disturbance. We perturbed intracarotid sinus pressure (CSP) according to a binary white noise sequence in anesthetized rabbits, while recording cardiac sympathetic nerve activity (SNA), arterial pressure (AP), and heart rate (HR). Intravenous administration of desipramine (1 mg/kg) decreased the normalized gain of the neural arc transfer function from CSP to SNA relative to untreated control (1.03 ± 0.09 vs. 0.60 ± 0.08 AU/mmHg, mean ± SE, P < 0.01) but did not affect that of the peripheral arc transfer function from SNA to AP (1.10 ± 0.05 vs. 1.08 ± 0.10 mmHg/AU). The normalized gain of the transfer function from SNA to HR was unaffected (1.01 ± 0.04 vs. 1.09 ± 0.12 beats·min-1·AU-1). Desipramine decreased the natural frequency of the transfer function from SNA to AP by 28.7 ± 7.0% (0.046 ± 0.007 vs. 0.031 ± 0.002 Hz, P < 0.05) and that of the transfer function from SNA to HR by 64.4 ± 2.2% (0.071 ± 0.003 vs. 0.025 ± 0.002 Hz, P < 0.01). In conclusion, neuronal NE uptake blockade by intravenous desipramine administration reduced the total buffering capacity of the arterial baroreflex mainly through its action on the neural arc. The differential effects of neuronal NE uptake blockade on the dynamic AP and HR responses to SNA may provide clues for understanding the complex pathophysiology of cardiovascular diseases associated with neuronal NE uptake deficiency.

Original languageEnglish
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number6 55-6
Publication statusPublished - Jun 1 2004
Externally publishedYes



  • Desipramine
  • Heart rate
  • Sympathetic nerve activity
  • Systems analysis
  • Transfer function

ASJC Scopus subject areas

  • Physiology

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