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

Research output: Contribution to journalArticle

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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 % O<inf>2</inf> 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 β<inf>1</inf>-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, β<inf>1</inf>-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 β<inf>1</inf>-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
Volume109
Issue number5
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Blood Vessels
Lung
Vasoconstrictor Agents
Metoprolol
Hypoxia
Pulmonary Circulation
Electrophysiology
Vasoconstriction
Vasodilator Agents
Adrenergic Agents
Adrenergic Receptors
Brain Stem
Air

Keywords

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

ASJC Scopus subject areas

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

Cite this

Pulmonary vascular tone is dependent on the central modulation of sympathetic nerve activity following chronic intermittent hypoxia. / Shirai, Mikiyasu; Tsuchimochi, Hirotsugu; Nagai, Hisashi; Gray, Emily; Pearson, James T.; Sonobe, Takashi; Yoshimoto, Misa; Inagaki, Tadakatsu; Fujii, Yutaka; Umetani, Keiji; Kuwahira, Ichiro; Schwenke, Daryl O.

In: Basic Research in Cardiology, Vol. 109, No. 5, 2014.

Research output: Contribution to journalArticle

Shirai, M, Tsuchimochi, H, Nagai, H, Gray, E, Pearson, JT, Sonobe, T, Yoshimoto, M, Inagaki, T, Fujii, Y, Umetani, K, Kuwahira, I & Schwenke, DO 2014, 'Pulmonary vascular tone is dependent on the central modulation of sympathetic nerve activity following chronic intermittent hypoxia', Basic Research in Cardiology, vol. 109, no. 5. https://doi.org/10.1007/s00395-014-0432-y
Shirai, Mikiyasu ; Tsuchimochi, Hirotsugu ; Nagai, Hisashi ; Gray, Emily ; Pearson, James T. ; Sonobe, Takashi ; Yoshimoto, Misa ; Inagaki, Tadakatsu ; Fujii, Yutaka ; Umetani, Keiji ; Kuwahira, Ichiro ; Schwenke, Daryl O. / Pulmonary vascular tone is dependent on the central modulation of sympathetic nerve activity following chronic intermittent hypoxia. In: Basic Research in Cardiology. 2014 ; Vol. 109, No. 5.
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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.",
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AU - Shirai, Mikiyasu

AU - Tsuchimochi, Hirotsugu

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AU - Gray, Emily

AU - Pearson, James T.

AU - Sonobe, Takashi

AU - Yoshimoto, Misa

AU - Inagaki, Tadakatsu

AU - Fujii, Yutaka

AU - Umetani, Keiji

AU - Kuwahira, Ichiro

AU - Schwenke, Daryl O.

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