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ASIC1 mediates enhanced receptor‐mediated vasoconstriction following chronic hypoxia‐induced pulmonary hypertension
Author(s) -
Jernigan Nikki L,
Walker Benjimen R,
Resta Thomas C
Publication year - 2010
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.24.1_supplement.1023.18
Subject(s) - vasoconstriction , hypoxic pulmonary vasoconstriction , endothelin receptor , vasodilation , pulmonary hypertension , vascular smooth muscle , medicine , endothelin 1 , hypoxia (environmental) , endocrinology , chemistry , receptor , cardiology , smooth muscle , organic chemistry , oxygen
Increases in pulmonary vascular smooth muscle (VSM) store‐operated Ca 2+ entry (SOCE) are implicated in augmented basal VSM intracellular Ca 2+ ([Ca 2+ ] i ) and enhanced vasoconstriction in chronic hypoxia (CH)‐induced pulmonary hypertensive rats. Our laboratory has recently characterized a unique role for acid sensing ion channel 1 (ASIC1) in regulating SOCE in pulmonary VSM. The goal of the present study was to determine the physiological importance of ASIC1‐mediated SOCE to receptor‐mediated pulmonary vasoconstriction. We hypothesized that enhanced Ca 2+ entry through ASIC1 contributes to increased receptor‐mediated vasoconstriction following CH. To test this hypothesis we examined vasoconstrictor and VSM [Ca 2+ ] i to UTP, endothelin‐1, KCl (depolarizing stimulus), and elevated intraluminal pressure (myogenic) in fura‐2‐loaded, endothelium‐disrupted, pressurized small pulmonary arteries from control and CH rats (4 wk at 0.5 atm). Specific inhibition of ASIC1 with psalmotoxin 1 (PcTX1) attenuated vasoconstriction and increases in VSM [Ca 2+ ] i to UTP and endothelin‐1 in arteries from control and CH rats; normalizing the responses between groups. However, PcTX1 had no effect on depolarization‐ or pressure‐induced vasoconstriction and changes in VSM [Ca 2+ ] i. These studies support a novel role of ASIC1 in elevated receptor‐stimulated vasoconstriction following CH which is likely mediated through increased SOCE.

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