Bioenergetics of liver mitochondria after administration of ramipril in experimental diabetes mellitus

BACKGROUND: Diabetes mellitus represents an intense metabolic strain for the liver. Inhibitors of angiotensin-converting enzymes (ACEI) are drugs of choice in the therapy of hypertension in coincidence with diabetes mellitus. The effect of ACEI is complex. The attention is drawn to the study of metabolic effects of ACEI. OBJECTIVES: The aim of the study was to investigate whether the administration of ramipril affects the levels of glycated hemoglobin and fructoseamine in the blood of rats with insulin-dependent diabetes mellitus (IDDM), and whether bioenergetics of mitochondria in the liver undergo changes. METHODS: In our experiments, we used rats of the Wistar strain. The control group was composed of healthy animals. The experimental groups were formed by rats with IDDM evoked by streptozotocine (45 mg/kg) and rats with IDDM + ramipril (10 mg/KG). Both, insulin MONO-ID in the doses of 6 U/kg administered subcutaneously, and water solution of ramipril administered by gastric probe were applied for the period of 8 weeks. We have assessed blood levels of glucose, glycated hemoglobin, fructoseamine and the concentration of cholesterol and triacylglycerols have been assessed also in the liver. Oxidative phosphorylation in mitochondria of the liver were measured polarographically. RESULTS: In the group with IDDM + ramipril, the glycated haemoglobin (M 6.85 CI 5.7-7.0%) and fructoseamine (M 1.45 CI 1.2-1.6 mmol/l) have significantly dropped in comparison with the group with IDDM glycated haemoglobin (M 8.8 7.7-10.7%) and fructoseamine (M 2.04 CI 1.69-2.4 mmol/l). Ramipril did not affect the concentration of cholesterol and triacylglycerols in the blood and liver in rats with IDDM. Ramipril has positively affected oxidative phosphorylation in mitochondria of the liver in coincidence with IDDM. The group with IDDM + ramipril has yielded an increase in the velocity of oxygen consumption in coincidence with stimulated breathing with ADP, the state 3 (M 107.97 CI 96.78-134.51 n AtO/mg of proteins/min.) and phosphorylation velocity (M 232.67 CI 209.38-284.97 nmolATP/protein/min) in contrast to the group with IDDM: the state 3 (M 76.71 CI 66.81-85.99 nAtO/mg of proteins/min and the velocity of phosphorylation (M 161.84 CI 143.55-189.99 nmol ATP/mg of proteins/min) in coincidence with substrate glutamate. A similar trend is present also in coincidence with FAD succinate substrate. CONCLUSIONS: After the administration of ramipril to rats with IDDM, the indicators have improved, and they express the rate of compensation of diabetes mellitus. An increased capacity of the respiratory chain and an increased origin of energy in mitochondria in the livers of rats with IDDM after administration of ramipril indicates an improvement in the metabolic capacity of the liver. (Tab. 4. Ref. 47.)