Introduction: 

We have been able to demonstrate earlier that the activation of the tissue renin-angiotensin system of the heart is related to disturbances in myocardial calcium homeostasis, which is an important factor in the development of heart complications. The aim of the present study was to examine if the same relationship exists in metabolic syndrome, characterized by a combination of insulin resistant diabetes mellitus and hypertension.

Methods: 

Male Sprague-Dawley rats were kept on high fructose diet for 10 weeks to induce metabolic syndrome. Starting with the third week of the diet, a group of the animals received ACE inhibitor enalapril treatment in depressor dose (20 mg/kg daily) delivered in the form of a subcutaneous biodegradable pellet in a period of 8 weeks. Another group received a sub-depressor dose (1.5 mg/kg daily) of the same drug. At the end of the treatment period echocardiography, blood pressure tests and oral glucose tolerance tests were performed, then isolated heart preparations were used to register left ventricular pressure and Ca²⁺ transients.

Results: 

The impaired glucose tolerance that developed following the high fructose diet was not influenced by either therapy. Hypertension was corrected by enalapril treatment in depressor dose, and was unaffected by sub-depressor dose therapy. With fructose feeding, heart muscle hypertrophy ensued, which was prevented by enalapril therapy in the depressor dose. In metabolic syndrome echocardiography demonstrated a decrease in pump function which was corrected by depressor dose

ACE inhibitor therapy, and ameliorated by the sub-depressor dose. The inotropic and lusitropic disturbances found in the hearts of fructose-fed animals were corrected by depressor dose ACE inhibitor treatment, and beneficially influenced by sub-depressor dose treatment. Analysis of the Ca²⁺ transients found decreased rates of Ca²⁺ release and sequestration, which were normalized by enalapril in both doses.

Conclusions: 

The cardiac dysfunction seen in metabolic syndrome in this model can be normalized by ACE inhibitor treatment adequate for correction of hypertension, but even sub-depressor dose ACE inhibitor therapy is beneficial. In our experiments, pathologic changes of the myocardial Ca²⁺ transient could be prevented even with the lesser dose of enalapril. Based on these findings it can be established that angiotensin II generated in the heart tissue in diabetic metabolic disorder has an important role in the development of impaired Ca²⁺ homeostasis.

Research supported by OTKA grant No. 68502