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Pde3a‐deficient mice have evidence of pulmonary hypertension
Author(s) -
Chen Bernadette,
Meng Xiaomei,
Jin Yi,
Nelin Leif D
Publication year - 2013
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.27.1_supplement.1140.12
Subject(s) - hypoxic pulmonary vasoconstriction , hypoxia (environmental) , ventricle , pulmonary hypertension , pulmonary artery , medicine , lung , ventricular pressure , endocrinology , vasoconstriction , cardiology , chemistry , hemodynamics , oxygen , organic chemistry
Pulmonary hypertension (PH) is associated with vasoconstriction and vascular remodeling characterized by pulmonary artery smooth muscle cell (PASMC) proliferation. In vitro , human PASMC proliferation requires arginase II (arg II) and cAMP elevating agents prevent hypoxia‐induced arg II induction. We hypothesized that Pde3a ‐deficient mice have attenuated PH. Pde3a−/− (KO) and wild type (WT) mice were exposed to 21%O 2 (normoxia) or 10%O 2 (hypoxia) for 28d. Right ventricle systolic pressure (RVSP) was measured. 2D echocardiography was used to measure pulmonary acceleration time/ejection time (PAT/PET). The mice were sacrificed; lungs and hearts were harvested. RV and left ventricle (LV)+septum (S) were weighed and ratio of RV/(LV+S) weights calculated. Lung arg II and cAMP levels were measured. KO mice had higher RVSP, lower PAT/PET ratios, and higher RV/(LV+S) ratios compared to WT mice. KO mice had greater lung cAMP, but arg II protein levels did not differ from WT mice. Interestingly, KO mice exposed to hypoxia had similar RVSP, PAT/PET and RV/(LV+S) ratios as hypoxia‐exposed WT mice. Pde3a ‐deficient mice have evidence of PH as seen by RVSP, PAT/PET and RV/(LV+S) ratios. Interestingly, hypoxia exposure did not result in any worsening of PH in KO mice. Our data suggest that alterations in Pde3a gene function may underlie forms of PH not associated with hypoxia, such as primary pulmonary arterial hypertension.