Effect of atorvastatin on intracellular calcium uptake in coronary smooth muscle cells from diabetic pigs fed an atherogenic diet.
Intracellular Ca(2+) store loading has been shown to alter proliferation and apoptosis of several cell types. In addition, HMG-CoA reductase inhibitors (i.e. atorvastatin) are effective in treating diabetic dyslipidemic patients. Thus, we hypothesized that chronic atorvastatin treatment would prevent increased Ca(2+) uptake into intracellular Ca(2+) stores in vascular smooth muscle cells from diabetic dyslipidemic pigs. Male Yucatan pigs were divided into four groups for 20 weeks-- (1) low fat fed (control); (2) hyperlipidemic (F); (3) alloxan-induced diabetic dyslipidemic (DF); and (4) diabetic dyslipidemic pigs treated with atorvastatin (DFA). The F, DF, and DFA groups were fed a high fat/cholesterol diet. Cells were isolated from the coronary artery and the myoplasmic Ca(2+) (Ca(m)) response measured using single cell fura-2 imaging. The Ca(m) response to caffeine (5 mM to release Ca(2+) from the sarcoplasmic reticulum, SR) and ionomycin (10 microM; to release the total Ca(2+) store) was determined in either the presence of low Na (19Na; inhibits Na(+)-Ca(2+) exchange), thapsigargin (TSG; inhibits the SR Ca(2+) pump), and a 19Na+TSG solution. Low Na induced the uptake of Ca(2+) into both SR and non-SR Ca(2+) stores in the DF group, but not the DFA group. Furthermore, after depletion of the SR Ca(2+) store with TSG, 19Na evoked Ca(2+) uptake into non-SR Ca(2+) stores in all three groups except in the DFA group. In summary, this study demonstrates that atorvastatin prevents the enhanced uptake of Ca(2+) by SR and non-SR Ca(2+) stores in diabetic dyslipidemic pigs.
Hill
B J
BJ
Department of Physiology, School of Medicine, University of Missouri, MA415 Medical Sciences Building, Columbia, MO 65212, USA. sturekm@missouri.edu
Dixon
J L
JL
Sturek
M
M
D000818:Animals; D000069059:Atorvastatin; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D004036:Diet, Atherogenic; D005456:Fluorescent Dyes; D016257:Fura-2; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000150:complications / Q000378:metabolism*; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012964:Sodium / Q000494:pharmacology; D013552:Swine; D013556:Swine, Miniature; D019284:Thapsigargin / Q000494:pharmacology
D005456:Fluorescent Dyes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007476:Ionophores; D011758:Pyrroles; D002110:Caffeine; D015759:Ionomycin; D019284:Thapsigargin; D012964:Sodium; D000069059:Atorvastatin; D002118:Calcium; D016257:Fura-2