Decrease in myocardial Na(+)-K(+)-ATPase activity and ouabain binding sites in hypercholesterolemic rabbits.
OBJECTIVE
The purpose of this study was to explore the effect of high dietary cholesterol on the lipid composition, Na(+)-K(+)-ATPase activity and ouabain receptor property of the myocardial sarcolemma.


METHODS
Male New Zealand white rabbits were fed with standard chow or standard chow supplemented with 0.5% (w/w) cholesterol and 10% (w/w) coconut oil to induce hypercholesterolemia. After 8 weeks, the rabbits were sacrificed; a myocardial sarcolemma fraction was then prepared from the left ventricular myocardium and analyzed for lipid composition. Assay of Na(+)-K(+)-ATPase activity and 3H-ouabain binding studies were performed in the myocardial sarcolemma from the control and cholesterol-fed rabbits.


RESULTS
The cholesterol content, but not the phospholipid content, of the sarcolemma was significantly greater in the cholesterol-fed group, thus, resulting in an increased cholesterol/phospholipid molar ratio in the cholesterol-fed group. In addition, a decrease in Na(+)-K(+)-ATPase activity was also found in this group. The decrease in Na(+)-K(+)-ATPase activity was selective, since the Mg(++)-ATPase and 5'-nucleotidase activities remained unchanged. In the 3H-ouabain binding study, a decrease in the number of maximum binding sites, but not the binding affinity, for 3H-ouabain was found in the cholesterol-fed group.


CONCLUSIONS
High dietary cholesterol induces higher levels of cholesterol not only in the plasma, but also in the myocardial sarcolemma. These changes result in decreased myocardial Na(+)-K(+)-ATPase activity mediated by a reduction in the maximum number of binding sites for ouabain but not a change in binding affinity.
Chen
W J
WJ
Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei.
Lin-Shiau
S Y
SY
Huang
H C
HC
Lee
Y T
YT
D015720:5'-Nucleotidase / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002784:Cholesterol / Q000032:analysis; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D006937:Hypercholesterolemia / Q000097:blood / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D010042:Ouabain / Q000378:metabolism*; D011817:Rabbits; D012508:Sarcolemma / Q000201:enzymology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D002791:Cholesterol, Dietary; C028996:cardiac glycoside receptors; D014284:Triiodothyronine; D010042:Ouabain; D002784:Cholesterol; D015720:5'-Nucleotidase; D000254:Sodium-Potassium-Exchanging ATPase; D013974:Thyroxine