Effect of diabetes on cytosolic free Ca2+ and Na(+)-K(+)-ATPase in rat aorta.
We examined Na(+)-K(+)-ATPase activity and the levels of alpha I-, alpha II-, and beta-subunit mRNA and protein in aortic cells of diabetic rats. Diabetes was induced by streptozocin. Na(+)-K(+)-ATPase activity was significantly reduced on the 2nd day of diabetes (9.4 +/- 1.3 vs. 17.5 +/- 2.1 mumol NADH.mg-1 protein.h-1, P less than 0.05) and remained depressed on days 7 and 14. The levels of 5.3-kilobase (kb) mRNA band of the catalytic alpha II-subunit of Na(+)-K(+)-ATPase were also decreased on the 2nd day of diabetes, whereas the second band, 3.4 kb, was not affected. Both bands were significantly decreased on days 7 and 14. This was followed by a reduction in the levels of alpha II-protein (day 14). The levels of alpha I- and beta-subunit mRNA and alpha I- protein were not affected by diabetes. A decrease in Na(+)-K(+)-ATPase activity was accompanied by a significant (P less than 0.001) increase in the cytosolic free Ca2+ concentrations [( Ca2+]i) in diabetic aortic cells (221 +/- 18 nM on the 7th day and 242 +/- 17 nM on the 14th day vs. 153 +/- 7 nM in controls). These findings are consistent with the hypothesis that decreased Na(+)-K(+)-ATPase activity and gene expression in vascular smooth muscle cells with accompanied rises in [Ca2+]i may be an important pathogenetic factor in the development of hypertension and atherosclerosis in diabetes.
Ohara
T
T
Medical Research Service, Veterans Affairs Medical Center, Denver, CO 80220.
Sussman
K E
KE
Draznin
B
B
D000818:Animals; D001011:Aorta / Q000201:enzymology* / Q000502:physiology / Q000648:ultrastructure; D015152:Blotting, Northern; D015153:Blotting, Western; D000252:Calcium-Transporting ATPases / Q000378:metabolism* / Q000502:physiology; D003600:Cytosol / Q000201:enzymology*; D003720:Densitometry; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D013311:Streptozocin
D012333:RNA, Messenger; D013311:Streptozocin; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase