Pulmonary vascular tone is dependent on the central modulation of sympathetic nerve activity following chronic intermittent hypoxia

Mikiyasu Shirai, Hirotsugu Tsuchimochi, Hisashi Nagai, Emily Gray, James T. Pearson, Takashi Sonobe, Misa Yoshimoto, Tadakatsu Inagaki, Yutaka Fujii, Keiji Umetani, Ichiro Kuwahira, Daryl O. Schwenke

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26 Citations (Scopus)


Chronic intermittent hypoxia (IH) provokes a centrally mediated increase in sympathetic nerve activity (SNA). Although this sympathetic hyperexcitation has been linked to systemic hypertension, its effect on the pulmonary vasculature is unclear. This study aimed to assess IH-mediated sympathetic excitation in modulating pulmonary vasculature tone, particularly acute hypoxia vasoconstrictor response (HPV), and the central β-adrenergic signaling pathway for facilitating the increase in SNA. Sprague–Dawley rats were exposed to IH (cycle of 4 % O2 for 90 s/air for 90 s) for 8 h/day for 6 weeks. Subsequently, rats were anesthetized and either pulmonary SNA was recorded (electrophysiology), or the pulmonary vasculature was visualized using microangiography. Pulmonary sympathetic and vascular responses to acute hypoxia were assessed before and after central β1-adrenergic receptor blockade (Metoprolol, 200 nmol i.c.v.). Chronic IH increased baseline SNA (110 % increase), and exacerbated the sympathetic response to acute hypoxia. Moreover, the magnitude of HPV in IH rats was blunted compared to control rats (e.g., 10 and 20 % vasoconstriction, respectively). In only the IH rats, β1-receptor blockade with metoprolol attenuated the hypoxia-induced increase in pSNA and exacerbated the magnitude of acute HPV, so that both sympathetic and HPV responses were similar to that of control rats. Interestingly, the expression of β1-receptors within the brainstem was similar between both control and IH rats. These results suggest that the centrally mediated increase in SNA following IH acts to blunt the local vasoconstrictor effect of acute hypoxia, which reflects an inherent difference between vasodilator and vasoconstrictor actions of SNA in pulmonary and systemic circulations.

Original languageEnglish
JournalBasic Research in Cardiology
Issue number5
Publication statusPublished - 2014 Sept 10
Externally publishedYes


  • Beta-adrenergic
  • Intermittent hypoxia
  • Pulmonary sympathetic nerve activity
  • Rat
  • Synchrotron radiation microangiography

ASJC Scopus subject areas

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


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