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 Ca(2+)- and Mg(2+)-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, Ca(2+)(-) and Mg(2+)-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, Mg(2+)-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 Ca(2+)- and Mg(2+)-ATPase activity in control animals.


CONCLUSIONS
The decrease in Mg(2+)-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 Ca(2+)- and Mg(2+)-activated ATPase activities from the fetus to adult could partially explain the previously found maturational increase in cardiac contractility.
Kamitomo
Masato
M
Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, California, USA.
Onishi
Junji
J
Gutierrez
Ivan
I
Stiffel
Virginia M
VM
Gilbert
Raymond D
RD
D000199:Actins / Q000032:analysis; D000531:Altitude; D000818:Animals; D015153:Blotting, Western; D017301:Ca(2+) Mg(2+)-ATPase / Q000032:analysis; D002118:Calcium / Q000008:administration & dosage; D000252:Calcium-Transporting ATPases / Q000032:analysis; D003285:Contractile Proteins / Q000032:analysis*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D000860:Hypoxia / Q000378:metabolism*; D008274:Magnesium / Q000008:administration & dosage; D009206:Myocardium / Q000737:chemistry*; D009210:Myofibrils / Q000201:enzymology; D009218:Myosins / Q000032:analysis; D011247:Pregnancy; D012756:Sheep; D020107:Troponin T / Q000032:analysis
D000199:Actins; D003285:Contractile Proteins; D020107:Troponin T; D017301:Ca(2+) Mg(2+)-ATPase; D009218:Myosins; D000252:Calcium-Transporting ATPases; D008274:Magnesium; D002118:Calcium