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Effects of Long-Term Hypoxia and Development on Cardiac Contractile Proteins in Fetal and Adult Sheep

Objective: We studied the effect of long-term, high-altitude hypoxia on cardiac myosin, actin, and troponin T (TnT) isoforms and Ca2+ and Mg2+-activated myofibrillar adenosine triphosphatase (ATPase) activities in fetal and adult sheep. Methods: We exposed pregnant (beginning at day 30 of gestation) and nonpregnant sheep to high altitude (3820 m) for 110 days. Myosin, actin, and TnT isoforms were analyzed by Western analysis. In purified myofibrillar preparations, Ca2+ and Mg2+-ATPase activities were measured by the appearance of inorganic phosphate after the addition of NaATP and various concentrations of either calcium or magnesium to the reaction mixture. Results: We found no change in myosin, actin, or TnT isoform composition after exposure to long-term hypoxia in either fetal or adult sheep. However, Mg2+-activated myofibrillar ATPase activity decreased significantly in the right ventricle of both fetus and adult after hypoxic exposure. There was also a significant maturational increase in both Ca2+ and Mg2+-ATPase activity in control animals. Conclusion: The decrease in Mg2+-activated myofibrillar ATPase activity might affect the decrease in cardiac contractility previously noted in the right ventricle of fetal sheep after exposure to long-term hypoxia. Likewise, the increase in Ca2+ and Mg2+-activated ATPase activities from the fetus to adult could partially explain the previously found maturational increase in cardiac contractility.