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Acute Hypoxia Alters Ryanodine Receptor Activity in Pulmonary Arterial Myocytes of High Altitude Acclimatized Fetal and Adult Sheep
Author(s) -
Thomas Jonathan,
Yoo Timothy,
Romero Monica,
Puglisi Jose,
Zhang Lubo,
Wilson Sean M.
Publication year - 2018
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.2018.32.1_supplement.892.5
Subject(s) - ryanodine receptor , hypoxia (environmental) , myocyte , fetus , medicine , endocrinology , pulmonary hypertension , hypoxic pulmonary vasoconstriction , biology , cardiology , chemistry , receptor , oxygen , pregnancy , organic chemistry , genetics
Intrauterine stress, such as long term high altitude hypoxia (LTH), can alter pulmonary function and reprogram fetal pulmonary vascular development, potentially causing respiratory distress and pulmonary hypertension after birth. Our recent data demonstrates that newborn LTH lambs exhibit exaggerated hypoxia‐induced pulmonary vasoconstriction (HPV). Previous evidence shows Ryanodine Receptor (RyR) activation is central to the HPV response. Furthermore, LTH disrupts RyR activated Ca 2+ sparks in pulmonary arterial (PA) myocytes of sheep. Given the relationship between RyR and HPV responses, we tested the hypothesis that acute hypoxia (exposure to 4% O 2 ) and LTH increase RyR mediated Ca 2+ spark activity. This was tested by measuring the Ca 2+ spark activity in PA myocytes of near‐term fetal lambs and adult sheep that resided at either low (335m, LA) or high (3801m, HA) altitude. Intracellular Ca 2+ was recorded in myocytes of isolated PA tissues loaded with Fluo‐4 using line‐scan techniques on a confocal microscope. Line‐scan images were analyzed using custom software (SparkLab) to determine the number of cells displaying sparks, spark frequency, and spatial‐ temporal characteristics. Adult myocytes had greater prevalence and frequency of Ca 2+ sparks relative to those of fetuses, confirming previous studies. Acute hypoxia significantly decreased spark prevalence and frequency in myocytes from both HA fetal and LA adult groups; however, acute hypoxia increased spark prevalence and frequency in HA adult sheep. Spark amplitude was decreased by acute hypoxia in the LA fetus but increased in the HA adult. Acute hypoxia also reduced spark duration in the fetus independent of altitude but increased the duration in HA adult. These results provide new insight into the influence of high altitude reprogramming of RyR function in PA of the fetus and adult and the roles their activity have during acute hypoxic exposures. Support or Funding Information This work is supported by The National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development grant number HD083132, by the National Science Foundation under Grant No. MRI 0923559, and the Loma Linda University School of Medicine. JT was a Loma Linda University Summer Undergraduate Research Fellow while TY was a Walter E Macpherson Society Medical Student Summer Research Fellow. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .