Therapeutic hypercapnia prevents chronic hypoxia-induced pulmonary hypertension in the newborn rat

Crystal Kantores; Patrick J McNamara; Lilian Teixeira; Doreen Engelberts; Prashanth Murthy; Brian P Kavanagh; Robert P Jankov

doi:10.1152/ajplung.00480.2005

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Therapeutic hypercapnia prevents chronic hypoxia-induced pulmonary hypertension in the newborn rat

Journal article

Peer reviewed

Therapeutic hypercapnia prevents chronic hypoxia-induced pulmonary hypertension in the newborn rat

Crystal Kantores, Patrick J McNamara, Lilian Teixeira, Doreen Engelberts, Prashanth Murthy, Brian P Kavanagh and Robert P Jankov

American journal of physiology. Lung cellular and molecular physiology, Vol.291(5), pp.L912-922

11/2006

DOI: 10.1152/ajplung.00480.2005

PMID: 16829630

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Abstract

Induction of hypercapnia by breathing high concentrations of carbon dioxide (CO(2)) may have beneficial effects on the pulmonary circulation. We tested the hypothesis that exposure to CO(2) would protect against chronic pulmonary hypertension in newborn rats. Atmospheric CO(2) was maintained at <0.5% (normocapnia), 5.5%, or 10% during exposure from birth for 14 days to normoxia (21% O(2)) or moderate hypoxia (13% O(2)). 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% CO(2) (but not to 5.5% CO(2)) significantly attenuated pulmonary vascular remodeling and increased pulmonary arterial resistance in hypoxia-exposed animals (P < 0.05), whereas both concentrations of CO(2) normalized right ventricular performance. Exposure to 10% CO(2) 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 CO(2) on the lung and consequent modulating effects on the endothelin pathway.

Body Weight

Hematocrit

Hypertension, Pulmonary - prevention & control

Hypertrophy, Right Ventricular - drug therapy

Hypoxia - metabolism

Pulmonary Artery - metabolism

Female

Hypertension, Pulmonary - drug therapy

Hypertrophy, Right Ventricular - metabolism

Endothelin Receptor Antagonists

Carboxylic Acids - pharmacology

Hypercapnia - metabolism

Animals, Newborn

Endothelin-1 - metabolism

Rats

Hypertension, Pulmonary - metabolism

Carbon Dioxide - blood

Oxygen - blood

Pregnancy

Up-Regulation - drug effects

Animals

Hypoxia - pathology

Hypertrophy, Right Ventricular - prevention & control

Pulmonary Circulation - drug effects

Oxidative Stress - drug effects

Carbon Dioxide - pharmacology

Chronic Disease

Pulmonary Artery - pathology

Indans - pharmacology

Details

Title: Subtitle: Therapeutic hypercapnia prevents chronic hypoxia-induced pulmonary hypertension in the newborn rat
Creators: Crystal Kantores - Clinical Integrative Biology, Sunnybrook Research Institute, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
Patrick J McNamara
Lilian Teixeira
Doreen Engelberts
Prashanth Murthy
Brian P Kavanagh
Robert P Jankov
Resource Type: Journal article
Publication Details: American journal of physiology. Lung cellular and molecular physiology, Vol.291(5), pp.L912-922
DOI: 10.1152/ajplung.00480.2005
PMID: 16829630
ISSN: 1040-0605
eISSN: 1522-1504
Grant note: 74506 / Canadian Institutes of Health Research
Language: English
Date published: 11/2006
Academic Unit: Stead Family Department of Pediatrics; Neonatology; Internal Medicine
Record Identifier: 9984093483302771

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