Effects of an intracellular Ca(2+) chelator on insulin resistance and hypertension in high-fat-fed rats and spontaneously hypertensive rats.

Abstract

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.

• Authors: Y J Jang, H J Ryu, Y O Choi, J G Lee, C Kim, C H Leem, C S Park
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 53 Issue 3 Pg. 269-72 (Mar 2004) ISSN: 0026-0495 [Print] United States
• PMID: 15015134 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 5,5'-dimethyl bis(o-aminophenoxy)ethane-N,N,N',N' tetraacetic acetoxymethyl ester
• Blood Glucose
• Chelating Agents
• Dietary Fats
• Egtazic Acid
• Calcium

Topics

• Animals
• Blood Glucose (metabolism)
• Calcium (metabolism)
• Chelating Agents (therapeutic use)
• Diet
• Dietary Fats (toxicity)
• Dose-Response Relationship, Drug
• Egtazic Acid (analogs & derivatives, therapeutic use)
• Glucose Clamp Technique
• Hypertension (drug therapy, etiology, genetics)
• Insulin Resistance (physiology)
• Male
• Muscle, Smooth, Vascular (drug effects)
• Rats
• Rats, Inbred SHR
• Rats, Sprague-Dawley