Evaluation of right coronary vascular dysfunction in severe pulmonary hypertensive rats using synchrotron radiation microangiography

Tadakatsu Inagaki, James T. Pearson, Hirotsugu Tsuchimochi, Daryl O. Schwenke, Shigeyoshi Saito, Takahiro Higuchi, Takeshi Masaki, Keiji Umetani, Mikiyasu Shirai, Yoshikazu Nakaoka

Research output: Contribution to journalArticlepeer-review

Abstract

Pulmonary hypertension (PH) causes cardiac hypertrophy in the right ventricle (RV) and eventually leads to RV failure due to persistently elevated ventricular afterload. We hypothesized that the mechanical stress on the RV associated with increased afterload impairs vasodilator function of the right coronary artery (RCA) in PH. Coronary vascular response was assessed using microangiography with synchrotron radiation (SR) in two well-established PH rat models, monocrotaline injection or the combined exposure to chronic hypoxia and vascular endothelial growth factor receptor blockade with Su5416 (SuHx model). In the SuHx model, the effect of the treatment with the nonselective endothelin-1 receptor antagonist (ERA), macitentan, was also examined. Myocardial viability was determined in SuHx model rats, using 18F-FDG Positron emission tomography (PET) and magnetic resonance imaging (MRI). Endothelium-dependent and endothelium-independent vasodilator responses were significantly attenuated in the medium and small arteries of severe PH rats. ERA treatment significantly improved RCA vascular function compared with the untreated group. ERA treatment improved both the decrease in ejection fraction and the increased glucose uptake, and reduced RV remodeling. In addition, the upregulation of inflammatory genes in the RV was almost suppressed by ERA treatment. We found impairment of vasodilator responses in the RCA of severe PH rat models. Endothelin-1 activation in the RCA plays a major role in impaired vascular function in PH rats and is partially restored by ERA treatment. Treatment of PH with ERA may improve RV function in part by indirectly attenuating right heart afterload and in part by associated improvements in right coronary endothelial function.

Original languageEnglish
Pages (from-to)H1021-H1036
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume320
Issue number3
DOIs
Publication statusPublished - Mar 2021

Keywords

  • Coronary circulation
  • Pulmonary arterial hypertension
  • Right heart failure
  • Synchrotron radiation microangiography

ASJC Scopus subject areas

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

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