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Acute Hypoxia and Ryanodine Receptor Activity in Pulmonary Arterial Myocytes of High Altitude Acclimatized Fetal and Adult Sheep
Author(s) -
Yoo Timothy,
Romero Monica,
Puglisi Jose,
Bers Donald,
Izu Leighton,
Longo Lawrence,
Wilson Sean
Publication year - 2015
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.29.1_supplement.662.2
Subject(s) - hypoxia (environmental) , ryanodine receptor , fetus , pulmonary hypertension , hypoxic pulmonary vasoconstriction , medicine , effects of high altitude on humans , myocyte , biology , cardiology , endocrinology , anatomy , chemistry , receptor , oxygen , pregnancy , organic chemistry , genetics
Long term high altitude hypoxic (LTH) exposure while in‐utero reprograms the fetal lung, increasing the prevalence of pulmonary hypertension after birth. Our recent data illustrate that hypoxia‐induced pulmonary vasoconstriction is exaggerated in LTH newborn lambs. Furthermore, ryanodine receptors (RYRs) are important to pulmonary arterial activity during acute hypoxia and altered by LTH. In this study we tested the hypothesis that LTH modifies RYR activation by acute hypoxia in the prenatal period. This was achieved 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 using line‐scan techniques on a Zeiss 710 confocal microscope. Images were analyzed using customized software (SparkLab), which outputs the number of cells with sparks, spark frequency and spatial‐ temporal characteristics. The number of cells with sparks in adult LA control was greater than fetal LA control and adult LA acute hypoxic groups. Acute hypoxia modestly decreased Ca 2+ spark frequency in fetal HA but increased adult HA. Significant differences in several factors associated with the spatial‐temporal relationships also were also found, although their role in modulating vascular contraction is unclear. These results support the premise that RYRs are affected by high altitude fetal reprogramming and, by extension, their activation due to acute hypoxia (NIH and NSF).