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Basic Research in Cardiology

, 109:432 | Cite as

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. SchwenkeEmail author
Original Contribution

Abstract

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.

Keywords

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

Notes

Acknowledgments

The synchrotron radiation experiments were performed at the BL28B2 in the SPring-8 with the approval of the Japan Synchrotron Radiation Research Institute (Proposal No. 2011A1305). This study was supported by the Department of Physiology, Otago University, New Zealand, and by Intramural Research Fund (22-2-3, 25-3-1) for Cardiovascular Diseases of National Cerebral and Cardiovascular Center, and a Grant-in Aid for Scientific Research (16659210, 20590242, 23650213, 23249038) from the Ministry of Education, Culture, Sports, Sciences, and Technology of Japan.

Conflict of interest

Concerning the material presented in this manuscript, there are no conflicts of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Mikiyasu Shirai
    • 1
  • Hirotsugu Tsuchimochi
    • 1
  • Hisashi Nagai
    • 2
  • Emily Gray
    • 3
  • James T. Pearson
    • 4
  • Takashi Sonobe
    • 1
  • Misa Yoshimoto
    • 1
  • Tadakatsu Inagaki
    • 1
  • Yutaka Fujii
    • 1
  • Keiji Umetani
    • 5
  • Ichiro Kuwahira
    • 6
  • Daryl O. Schwenke
    • 3
    Email author
  1. 1.Department of Cardiac PhysiologyNational Cerebral and Cardiovascular Center Research InstituteSuitaJapan
  2. 2.Department of Forensic MedicineUniversity of TokyoTokyoJapan
  3. 3.Department of Physiology-Heart OtagoUniversity of OtagoDunedinNew Zealand
  4. 4.Monash Biomedical Imaging Facility, Department of PhysiologyMonash UniversityMelbourneAustralia
  5. 5.Japan Synchrotron Radiation Research InstituteHyogoJapan
  6. 6.Department of Respiratory MedicineTokai University School of MedicineTokyoJapan

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