Effects of an intracellular Ca(2+) chelator on insulin resistance and hypertension in high-fat-fed rats and spontaneously hypertensive rats.
We explored the possibility that a sustained elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)) may be a cellular abnormality common to both insulin resistance and hypertension. In high-fat diet (HFD) fed rats, the steady-state glucose infusion rate (GIR) during the euglycemic hyperinsulinemic clamp was reduced by 40% (P <.05) and mean arterial pressure (MAP) was elevated by 20 mm Hg (P <.01) in comparison to the normal chow-fed rats. Intravenous injection of 5,5'-dimethyl derivative of bis(o-aminophenoxy)ethane-N,N,N',N' tetraacetic acetoxymethyl ester (dimethyl-BAPTA/AM), an effective intracellular Ca(2+) chelator, 90 minutes before the clamp not only restored about 50% of the reduced GIR, but also normalized MAP in the HFD rats. The chelator injection also significantly increased GIR by 25% (P <.01) and reduced MAP about 30 mm Hg (P <.01) in the spontaneously hypertensive rats (SHR). In addition, we have recently shown in the HFD rats that an injection of dimethyl-BAPTA/AM normalizes elevated [Ca(2+)](i) in adipocytes. These results together demonstrate that lowering [Ca(2+)](i) simultaneously ameliorates both insulin resistance and hypertension and provide presumptive evidence that sustained high levels of [Ca(2+)](i) may play a common pathophysiologic role in these 2 diseases.
Jang
Y J
YJ
Department of Physiology, University of Ulsan College of Medicine, Seoul, Korea.
Ryu
H J
HJ
Choi
Y O
YO
Lee
J G
JG
Kim
C
C
Leem
C H
CH
Park
C S
CS
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002614:Chelating Agents / Q000627:therapeutic use*; D004032:Diet; D004041:Dietary Fats / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D015309:Glucose Clamp Technique; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley
C460021:5,5'-dimethyl bis(o-aminophenoxy)ethane-N,N,N',N' tetraacetic acetoxymethyl ester; D001786:Blood Glucose; D002614:Chelating Agents; D004041:Dietary Fats; D004533:Egtazic Acid; D002118:Calcium