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.