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Contribution of ASIC1 to development of right ventricular hypertrophy and pulmonary hypertension following chronic hypoxia
Author(s) -
Beasley Britta F,
Bosc Laura V Gonzalez,
Resta Thomas C,
Walker Benjimen R,
Jernigan Nikki L
Publication year - 2011
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.25.1_supplement.1034.18
Subject(s) - pulmonary hypertension , right ventricular hypertrophy , medicine , cardiology , ventricle , hypoxia (environmental) , muscle hypertrophy , hematocrit , chemistry , oxygen , organic chemistry
Chronic hypoxia (CH) associated with respiratory disease often results in pulmonary arterial constriction and vascular remodeling, ultimately leading to pulmonary hypertension and right heart failure. Several studies show increased vascular smooth muscle Ca 2+ influx mediates both the vasoconstrictor and vascular remodeling responses to CH. Our laboratory has recently demonstrated a role for acid‐sensing ion channel 1 (ASIC1) in mediating Ca 2+ entry in pulmonary vascular smooth muscle. In addition, pulmonary vascular ASIC1 protein is elevated following CH. Therefore, we hypothesize ASIC1 contributes to the development of pulmonary hypertension. To test this hypothesis we examined 1) right ventricular systolic pressure (RVSP) as an indicator of pulmonary arterial pressure, 2) right ventricle to total heart weight (RV/T) and RV to body weight (RV/BW) ratios to assess right ventricular hypertrophy, and 3) hematocrit to determine the degree of polycythemia in control and CH (4wk @ 0.5 atm) ASIC1 +/+ and ASIC1 −/− mice. As expected, CH increased these variables in both ASIC1 +/+ and ASIC1 −/− mice, however ASIC1 −/− CH mice displayed decreased RVSP, diminished RV/T and RV/BW ratio, and decreased hematocrit compared to ASIC1 +/+ CH mice. These data suggest that ASIC1 plays a significant role in the development of CH‐induced right ventricular hypertrophy and pulmonary hypertension.