Open AccessThe Na + /H + exchanger contributes to increased smooth muscle proliferation and migration in a rat model of pulmonary arterial hypertension
Author(s) -
Huetsch John C.,
Jiang Haiyang,
Larrain Carolina,
Shimoda Larissa A.
Publication year - 2016
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12729
Subject(s) - hypoxia (environmental) , pulmonary hypertension , intracellular ph , downregulation and upregulation , homeostasis , chemistry , vascular remodelling in the embryo , intracellular , medicine , cell growth , vascular smooth muscle , endocrinology , sodium–hydrogen antiporter , smooth muscle , biochemistry , oxygen , sodium , organic chemistry , gene
Increased muscularity of small pulmonary vessels, involving enhanced proliferation and migration of pulmonary arterial smooth muscle cells ( PASMC s), is a key component of the vascular remodeling underlying the development of pulmonary hypertension ( PH ). Stimuli such as growth factors and hypoxia induce PASMC alkalinization, proliferation, and migration through upregulation of the Na + /H + exchanger ( NHE ), inhibition of which prevents the development of hypoxia‐induced vascular remodeling and PH . We wanted to explore whether NHE was also necessary for pathologic PASMC proliferation and migration in a model of pulmonary arterial hypertension ( PAH ), a severe form of PH not associated with persistent hypoxia. PASMC s were isolated from rats exposed to SU 5416‐hypoxia ( SuHx ) followed by return to normoxia and from vehicle controls. We measured resting intracellular pH ( pH i ) and NHE activity using the pH ‐sensitive fluorescent dye BCECF ‐ AM . PASMC proliferation and migration were assessed using BrdU incorporation and transwell filters, respectively. NHE activity was increased in SuHx PASMC s, although resting pH i was unchanged. SuHx PASMC s also exhibited increased proliferation and migration relative to controls, which was attenuated in the setting of pharmacologic inhibition of NHE . Our findings suggest that increased NHE activity contributes to pathologic PASMC function in the SuHx model of PAH , although this effect does not appear to be mediated by global changes in pH i homeostasis.