Ryanodine Receptor 1 mRNA Expression is Increased by Post‐Natal Maturation and Long Term Hypoxia in Sheep Pulmonary Arteries

Abstract

Ryanodine receptors (RyRs) are well regarded for being important to vasorelaxation that occurs during the birth transition and with hypoxic pulmonary vasoconstrictor responses. Previous studies from our group show that RyR mediated Ca2+ spark events are suppressed in fetal pulmonary arterial myocytes and that these events are significantly modified by exposure to long term high altitude hypoxia. To begin to resolve the molecular underpinnings of these physiological responses we performed quantitative real time PCR for mRNA expression of the RyR1 isoform, which is one of three relevant isoforms that are likely to be expressed in pulmonary arterial myocytes. Pulmonary arterial (PA) segments were isolated from near‐term fetal or adult sheep housed at low altitude (300m) or exposed to high altitude (3,801m) for over 100 days. Comparisons of RyR1 mRNA expression were then made to the housekeeping gene beta‐actin. Based on these preliminary studies we found that the ΔCt for RyR1 mRNA expression relative to beta actin was significantly lower in the fetus relative to the adult independent of altitude. The ΔΔCt corresponded to a 12–17 fold increase in RyR1 mRNA expression due to maturation, which potentially accounts for previously shown maturational related enhancements in Ca2+ spark activity. Altitude caused a 2.8 fold increase in RyR1 mRNA expression in adult PA that correlate with previously shown maturational induced increases in spark activity. Interestingly, a 3.8 fold increase in RyR1 mRNA expression observed in fetal PA following hypoxia did not correspond to the hypoxia‐related depression in Ca2+ spark activity that we previously reported. Overall, these preliminary studies show pronounced changes in RyR1 mRNA expression that are likely to be important drivers of pulmonary vascular development as well as underlie pathologies due to long term high altitude exposure.Support or Funding InformationThis work is supported by The National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development grant number HD083132 and HD069746.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.