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Obesity Exacerbates the Development of Hypoxia‐induced Pulmonary Hypertension
Author(s) -
Irwin David C.,
Crossno Joseph,
Foreman Benjamin,
Sullivan Timothy,
Klemm Dwight
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb113-a
Subject(s) - medicine , pulmonary hypertension , ventricle , hypoxia (environmental) , endocrinology , pulmonary artery , obesity , cardiology , blood pressure , hemodynamics , chemistry , organic chemistry , oxygen
Obesity is a known risk factor for cardiovascular disease, insulin resistance and premature death. Recent observations from examining past medical records suggest that obesity may be a risk factor for the development of severe pulmonary hypertension. Therefore, we hypothesized that hypoxic pulmonary hypertension (PH) would be exacerbated in the Zucker obese vs. the Zucker lean rats. Methods: Male, age matched (8–10 wk) obese (547 ± 17 g) and lean (345 ± 11g) Zucker rats were exposed to either chronic hypoxia (3 wk; 18,000 ft; P B ~ 379 mm Hg;) or remained at ambient barometric pressure (5,280 ft; P B ~ 620 mm Hg). After wards, cardiac output (CO), mean pulmonary artery (Pa) and mean systemic pressures (MAP) and hemotocrit (Hct) were recorded. Following hemodynamic measurements, rats were euthanized, the lungs perfused with paraformaldehyde (PFA), dissected free of the heart and embedded in paraffin for histological analyses. The heart was removed, the right ventricle (RV) was dissected free from the left ventricle + septum (LV+S) and RV/LV+S ratio was determined as a further indication of the severity of PH. Results: Chronic hypoxia exposure increased Pa pressure, RV/ LV+S and Hct in all rats (P<0.001; P<0.01 and <0.001 vs. normoxia respectively). The Pa pressure, RV/LV+S were 37 ± 10%, 30 ± 12% and 18 ± 3% greater in the Zucker obese rats vs. Zucker lean cohorts (P=0.023; P=0.026 and P<0.01 respectively). Histological analyses revealed increased pulmonary remodeling in the obese vs. lean hypoxic rats. Conclusion: We conclude that obesity exacerbates hypoxia‐induced mean Pa pressure, right ventricular hypertrophy and pulmonary vascular remodeling.