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Role of Na+/H+ Exchange (NHE) in hypoxia‐induced pulmonary arterial smooth muscle cell (PASMC) growth and migration
Author(s) -
Undem Clark,
Walker Jasmine,
Shimoda Larissa A
Publication year - 2009
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.23.1_supplement.619.7
Subject(s) - hypoxia (environmental) , in vivo , pulmonary hypertension , ex vivo , cell growth , chemistry , cell migration , vascular remodelling in the embryo , microbiology and biotechnology , endocrinology , medicine , cell , biology , biochemistry , oxygen , organic chemistry
In many lung diseases, chronic hypoxia (CH) causes pulmonary hypertension resulting in part from vascular remodeling due to growth/migration of PASMCs. The mechanisms involved in this process are unresolved, but a role for NHE activity has been suggested. We examined whether NHE activity was required for hypoxia‐induced PASMC growth/migration. Equal numbers of PASMCs from rats exposed to normoxia or CH (10% O 2 ; 3 wk) were plated into 96 well plates (proliferation) or onto transwell filters (migration). In some experiments, cells were exposed to hypoxia (4 or 1% O2) ex vivo. PASMCs were cultured with or without the NHE inhibitor, ethyl isopropyl amiloride (EIPA; 10‐5 M). For proliferation, cells were cultured for 48 hr before addition of BrdU for 24 hrs. ELISA for BrdU incorporation showed that CH and ex vivo hypoxia induced PASMC proliferation. EIPA reduced both basal and hypoxia‐induced growth. For migration, PASMCs were cultured on filters for 24 hr, fixed and Coomasie stained. Cells on the transparent filters were imaged (total), the upper side of the filter scraped and images of migrated cells (bottom of filter) obtained. The percent of migrated cells was greater in cells exposed to CH and hypoxia ex vivo. EIPA reduced migration induced by CH and 4% O2. These data suggest that NHE activity modulates hypoxia‐induced PASMC growth and migration and may contribute to increased muscularization of small pulmonary arteries.