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Acute Hypoxia and Ryanodine Receptor Activity in Pulmonary Arterial Myocytes of High Altitude Acclimatized Fetal and Adult Sheep
Author(s) -
Goyenaga Geraldine,
Yoo Timothy,
Romero Monica,
Puglisi Jose,
Longo Lawrence D,
Wilson Sean M
Publication year - 2016
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.30.1_supplement.774.6
Subject(s) - hypoxia (environmental) , ryanodine receptor , fetus , hypoxic pulmonary vasoconstriction , medicine , myocyte , endocrinology , cardiology , vasoconstriction , biology , chemistry , receptor , oxygen , pregnancy , organic chemistry , genetics
Exposure to high altitude long term hypoxia (LTH) during the gestational period causes reprogramming of the fetal lung, increasing the likelihood of pulmonary hypertension. There is also regional acute hypoxia in the lung that causes hypoxia‐induced pulmonary vasoconstriction (HPV). This is an important process necessary to sustain arterial oxygenation. Further, ryanodine receptors (RYRs) play an important role in acute hypoxia through HPV and their function is reduced by LTH. In this study, we hypothesized that LTH would alter the activation of RyR by acute hypoxia. This was tested by measuring Ca 2+ spark activity in pulmonary arterial (PA) myocytes of fetal and adult sheep, where PAs were isolated from sheep that resided at either low (335m, LA) or high (3801m, HA) altitude for <100 days. Ca 2+ imaging was performed by loading cells with Fluo‐4 and imaging en‐face using line‐scan techniques on a Zeiss 710 confocal microscope. Images were analyzed using a customized software that allowed for detailed measurements of the frequency and spatial‐temporal aspects to the Ca 2+ sparks. Results showed that acute hypoxia affected Ca 2+ signaling in several ways. Specifically, the number of cells firing sparks increased in fetal myocytes at both elevations and in HA but not LA adults. In addition, Ca 2+ spark frequency significantly decreased in LA and HA fetuses. Spark frequency decreased in LA adults; which contrasts a frequency increase in HA adults. Aside from these results, distinct differences in the spatial and temporal relationships of Ca 2+ sparks were also observed. In conclusion, these findings support the proposition that high altitude fetal reprogramming affects RyR activity and acute hypoxia modifies their activation. Support or Funding Information Support from NIH, NSF, and the Walter E. Macpherson Society