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Maternal chronic hypoxic stress influences the role of extracellular Ca2+ influx to serotonin‐mediated contractility of pulmonary arteries from fetal sheep
Author(s) -
Goyal Ravi,
Vemulakonda Srilakshmi,
Mittal Ashwani,
Loftin Matthew,
Vranken Kurt,
Nguyen Dan,
Webster Melissa,
Blood Arlin B,
Pearce William J,
Longo Lawrence D,
Wilson Sean M
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.619.4
Subject(s) - contractility , extracellular , medicine , endocrinology , electrical impedance myography , nifedipine , fetus , chemistry , contraction (grammar) , vasoconstriction , hypoxia (environmental) , pulmonary hypertension , calcium , biology , vasodilation , biochemistry , pregnancy , oxygen , organic chemistry , genetics
Cytosolic Ca 2+ is central to pulmonary vascular reactivity and important to pathogenesis due to hypoxic stress, but the role of Ca 2+ to disease in the unborn fetus is not well understood. We therefore tested the hypothesis that chronic maternal hypoxia (CH) alters Ca 2+ ‐dependent contractility using wire‐myography and Western immunoblot of pulmonary arteries (PA) isolated from late gestational fetal sheep, where ewes were housed under normoxic conditions or at 12,470 feet for ~ 110 days (CH). Serotonin (5‐HT; 10 μM) dependent contractility was dependent on extracellular Ca 2+ in PA from both groups and 10 mM Ni 2+ inhibited contractility in CH. However, select Ca 2+ entry pathways were altered by CH. The role L‐type Ca 2+ channels was lessened by CH as indicated by diminutive action of 10 μM nifedipine (NIF) and reduced α‐subunit protein expression. The role for non‐selective cation channels was also reduced by CH, as determined by serial application of 50 μM SKF 96365 to NIF treated arteries. In comparison, reverse mode‐Na + ‐ Ca 2+ exchange had little role to the contractility response as 10 μM KB‐R7943 failed to reduce contractility. Given that extracellular Ca 2+ removal and Ni 2+ effectively reduced contractility while NIF, SKF, and KBR were ineffective, Ni 2+ but not SKF sensitive basal Ca 2+ influx may have a greater role during 5‐HT‐dependent contractility in fetal PA from CH sheep. Support from NIH, UM, and LLUMC.