Journal of Anesthesia

, Volume 29, Issue 5, pp 715–723 | Cite as

Sarpogrelate hydrochloride, a serotonin 5HT2A receptor antagonist, ameliorates the development of chronic hypoxic pulmonary hypertension in rats

  • Erquan Zhang
  • Junko Maruyama
  • Ayumu Yokochi
  • Yoshihide Mitani
  • Hirofumi Sawada
  • Masakatsu Nishikawa
  • Ning Ma
  • Kazuo Maruyama
Original Article
First Online:
Received:
Accepted:

Abstract

Purpose

The purpose of the present study was to determine if sarpogrelate hydrochloride (SPG), a serotonin 5HT2A receptor antagonist, prevented the development of chronic hypoxia-induced pulmonary hypertension (PH) and hypertensive pulmonary vascular remodeling.

Methods

Forty-one male Sprague–Dawley rats were exposed to hypobaric hypoxia (380 mmHg, 10 % oxygen) or room air and administered 50 mg/kg SPG or vehicle by gavage once daily from day −2 to day 14. The mean pulmonary artery pressure (PAP) and right ventricular hypertrophy (RVH) were measured. Hypertensive pulmonary vascular remodelings were assessed morphometrically by light microscopy. Serotonin-induced contraction was determined in isolated pulmonary artery rings from 24 rats. In another set of rats, Western blotting, real-time polymerase chain reaction and immunofluorescent staining (n = 9) for lung tissue were performed.

Results

Chronic hypoxia induced a rise in mean PAP and RVH, increased the percentage of muscularized arteries in peripheral pulmonary arteries and medial wall thickness in small muscular arteries, and potentiated serotonin-induced contraction, each of which was significantly (p < 0.05) ameliorated by SPG. Chronic hypoxia significantly increased the expression of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (peNOS) protein levels, cyclic guanosine monophosphate, and matrix metalloproteinase-13 (MMP-13) mRNA levels in whole lung tissues. SPG increased peNOS expression in the immunofluorescent staining of peripheral pulmonary arteries from chronic hypoxic rats and decreased the MMP-13 mRNA in lung tissue in chronic hypoxic rats.

Conclusions

The administration of SPG ameliorated the development of chronic hypoxic PH and hypertensive pulmonary vascular changes.

Keywords

Pulmonary hypertension Hypoxia Nitric oxide Sarpogrelate hydrochloride Serotonin 2A receptor 
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Notes

Acknowledgments

This study was supported in part by Grants-In-Aid for Scientific Research from the Japanese Association for the Promotion of Science. The authors thank Ms. A Okada and N Hiramtsu for the technical and secretarial assistance.

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Copyright information

© Japanese Society of Anesthesiologists 2015

Authors and Affiliations

  • Erquan Zhang
    • 1
  • Junko Maruyama
    • 1
    • 4
  • Ayumu Yokochi
    • 1
  • Yoshihide Mitani
    • 2
  • Hirofumi Sawada
    • 1
    • 2
  • Masakatsu Nishikawa
    • 3
  • Ning Ma
    • 5
  • Kazuo Maruyama
    • 1
  1. 1.Department of Anesthesiology and Critical Care MedicineMie University School of MedicineTsuJapan
  2. 2.Department of PediatricsMie University school of MedicineTsuJapan
  3. 3.Department of Institute of Human Research Promotion and Drug DevelopmentMie University school of MedicineTsuJapan
  4. 4.Faculty of Medical EngineeringSuzuka University of Medical ScienceSuzukaJapan
  5. 5.Faculty of Health ScienceSuzuka University of Medical ScienceSuzukaJapan

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