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Serotonin‐mediated Ca2+ signaling in pulmonary arterial myocytes and the combined influence of maturation and high‐altitude exposure
Author(s) -
Dawson Antoinette,
Osman Noah,
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.619.11
Subject(s) - contractility , endocrinology , hypoxia (environmental) , medicine , fetus , basal (medicine) , lung , serotonin , biology , myocyte , chemistry , receptor , oxygen , pregnancy , genetics , organic chemistry , insulin
The pulmonary vasculature regulates lung blood flow in order to maintain blood oxygenation. However, chronic hypoxia (CH) such as that induced by high‐altitude exposure leads to changes and dysfunctions in the pulmonary vasculature. Serotonin (5‐HT) is an inflammatory mediator that triggers cytosolic Ca 2+ increases and pulmonary arterial smooth muscle cell (PASMC) contractility. We have recently shown maturation and CH‐stress alters Ca 2+ ‐dependent contractility in pulmonary arteries from sheep. The present study extends these findings by testing two hypotheses, these being that maturation enhances while CH reduces 5‐HT ‐generated Ca 2+ signaling in sheep PASMCs. These hypotheses were assessed by performing confocal fluorescence microscopy of fluo‐4 in PASMCs in‐situ from fetal and adult sheep that were housed under normoxic conditions or at 12,470 feet (CH) for ~ 110 days. Basal Ca 2+ activity was greater in adult than fetus and in CH‐adults as compared to their normoxic counterparts. In the presence of 10 μM 5‐HT, adult PASMCs from CH and normoxic sheep had similar firing rates. However, 5‐HT‐mediated cell firing was blunted in PASMCs from CH fetus. Maturation of PASMCs from normoxic sheep resulted in increased basal and 5‐HT‐elicited Ca 2+ ‐ reactivity. These findings provide the first evidence that maturation and CH interact to alter 5‐HT‐dependent Ca 2+ signaling. Support from NSF, NIH, UM, and LLUMC.