Alterations in cardiac function and subcellular membrane activities after hypervitaminosis D3.
The present study was designed to induce massive accumulation of calcium in the myocardium and to evaluate the effect of calcium overload on myocardial contractile function and biochemical activity of cardiac subcellular membranes. Rats were treated with an oral administration of 500,000 units/kg of vitamin D3 for 3 consecutive days, and their hearts were sampled on the 5th day for biochemical analysis. On the 4th and 5th days, heart rate, mean aortic pressure, left ventricular systolic pressure and left ventricular dP/dt were significantly lowered in vitamin D3-treated rats, demonstrating the existence of appreciable myocardial contractile dysfunction. Marked increases in the myocardial calcium (67-fold increase) and mitochondrial calcium contents (24-fold increase) were observed by hypervitaminosis D3. Mitochondrial oxidative phosphorylation and ATPase activity were significantly reduced by this treatment. A decline in sarcolemmal Na+, K(+)-ATPase activity was also observed, while relatively minor or insignificant changes in calcium uptake and ATPase activities of sarcoplasmic reticulum were detectable. Electron microscopic examination revealed calcium deposits in the mitochondria after vitamin D3 treatment. The results suggest that hypervitaminosis D3 produces massive accumulation of calcium in the myocardium, particularly in the cardiac mitochondrial membrane, which may induce an impairment in the mitochondrial function and eventually may lead to a failure in the cardiac contractile function.
Takeo
S
S
Department of Pharmacology, Tokyo College of Pharmacy, Japan.
Tanonaka
R
R
Tanonaka
K
K
Miyake
K
K
Hisayama
H
H
Ueda
N
N
Kawakami
K
K
Tsumura
H
H
Katsushika
S
S
Taniguchi
Y
Y
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D010085:Oxidative Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D012508:Sarcolemma / Q000187:drug effects / Q000648:ultrastructure
D002762:Cholecalciferol; D000251:Adenosine Triphosphatases; D002118:Calcium