Drag-reducing polymers attenuates pulmonary vascular remodeling and right ventricular dysfunction in a rat model of chronic hypoxia-induced pulmonary hypertension

Induction of hypercapnia by breathing high concentrations of carbon dioxide (CO2) may have beneficial effects on the pulmonary circulation. We tested the hypothesis that exposure to CO2 would protect against chronic pulmonary hypertension in newborn rats. Atmospheric CO2 was maintained at <0.5% (normocapnia), 5.5%, or 10% during exposure from birth for 14 days to normoxia (21% O2) or moderate hypoxia (13% O2). Pulmonary vascular and hemodynamic abnormalities in animals exposed to chronic hypoxia included increased pulmonary arterial resistance, right ventricular hypertrophy and dysfunction, medial thickening of pulmonary resistance arteries, and distal arterial muscularization. Exposure to 10% CO2 (but not to 5.5% CO2) significantly attenuated pulmonary vascular remodeling and increased pulmonary arterial resistance in hypoxia-exposed animals ( P < 0.05), whereas both concentrations of CO2 normalized right ventricular performance. Exposure to 10% CO2 attenuated increased oxidant stress induced by hypoxia, as quantified by 8-isoprostane content in the lung, and prevented upregulation of endothelin-1, a critical mediator of pulmonary vascular remodeling. We conclude that hypercapnic acidosis has beneficial effects on pulmonary hypertension and vascular remodeling induced by chronic hypoxia, which we speculate derives from antioxidant properties of CO2 on the lung and consequent modulating effects on the endothelin pathway.

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P5417Serum levels of fetal tenascin-C variants as novel biomarkers reflecting vascular remodeling and right ventricular dysfunction in pulmonary hypertension

European Heart Journal ◽

10.1093/eurheartj/ehx493.p5417 ◽

2017 ◽

Vol 38 (suppl_1) ◽

Author(s):

M. Franz ◽

I. Rohm ◽

K. Gruen ◽

L.M. Mueller ◽

D. Kretzschmar ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Right Ventricular ◽

Vascular Remodeling ◽

Ventricular Dysfunction ◽

Right Ventricular Dysfunction ◽

Tenascin C ◽

Novel Biomarkers

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ETA-receptor antagonist prevents and reverses chronic hypoxia-induced pulmonary hypertension in rat

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1995.269.5.l690 ◽

1995 ◽

Vol 269 (5) ◽

pp. L690-L697 ◽

Cited By ~ 38

Author(s):

V. S. DiCarlo ◽

S. J. Chen ◽

Q. C. Meng ◽

J. Durand ◽

M. Yano ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Right Ventricular ◽

Receptor Antagonist ◽

Vascular Remodeling ◽

Ventricular Hypertrophy ◽

Chronic Hypoxia ◽

Right Ventricular Hypertrophy ◽

Pulmonary Vascular Remodeling ◽

Eta Receptor ◽

Eta Receptor Antagonist

The selective endothelin-A (ETA)-receptor antagonist BQ-123 has been shown to prevent chronic hypoxia-induced pulmonary hypertension in the rat. Therefore in the current study we utilized BQ-123 to test the hypothesis that blockade of the ETA receptor can reverse as well as prevent the increase in mean pulmonary artery pressure, right ventricle-to-left ventricle plus septum ratio, and percent wall thickness in small (50-100 microns) pulmonary arteries observed in male Sprague-Dawley rats exposed to normobaric hypoxia (10% O2, 2 wk). Infusion of BQ-123 (0.4 mg.0.5 microliter-1.h-1 for 2 wk in 10% O2) begun after 2 wk of hypoxia significantly reversed the established pulmonary hypertension and prevented further progression of right ventricular hypertrophy during the third and fourth week of hypoxia. BQ-123 infusion instituted before exposure to hypoxia completely prevented the hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary vascular remodeling. These findings suggest that, in the lung, hypoxia induced an increase synthesis of endothelin-1, which acts locally on ETA receptors to cause pulmonary hypertension, right heart hypertrophy, and pulmonary vascular remodeling, while ETA-receptor blockade can both prevent and reverse these processes.

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