ACUTE ADMINISTRATION OF METOPROLOL AND ENALAPRILAT REDUCES INSULIN-STIMULATED THERMOGENESIS AND SKIN BLOOD-FLOW

Objective. To examine the acute effects of intravenous metoprolol and enalaprilat on energy expenditure, thermogenesis, blood flow and insul in sensitivity. Design. Randomized, single-blind, placebo-controlled t rial. Setting. Helsinki University Central Hospital, Finland. Subjects . Seven moderately insulin-resistant nondiabetic subjects. Interventio ns. Each subject was studied three times at 2-3 weeks intervals; metop rolol (5 mg), enalaprilat (2 mg) or saline infusions were used. Method s. A 150-min euglycaemic/hyperinsulinaemic clamp combined with indirec t calorimetry and blood flow measurements were performed. Main outcome measures. Glucose uptake, forearm and skin blood flow, and energy exp enditure. Results. Blood pressure was decreased to the same degree by both drugs. Forearm blood flow (plethysmography) was lower with metopr olol compared to enalaprilat (2.1 +/- 0.2 vs. 2.8 +/- 0.4 mL per 100 m L min(-1); P < 0.05). Glucose-plus-insulin-stimulated thermogenesis an d total energy expenditure were reduced both by metoprolol (71 and 5.2 %; P < 0.05 in both) and enalaprilat (59%, P = 0.06; and 7.6%, P < 0.0 5) as compared to the control study. Skin blood flow (laser Doppler) i ncreased by 100% (P < 0.01) during the glucose-plus-insulin infusion, but this increment was inhibited by both drug infusions. Forearm and w hole-body glucose uptake was not influenced by metoprolol or enalapril at administration. Conclusions. (i) Both metoprolol and enalaprilat in hibit glucose-plus-insulin-induced thermogenesis and a rise in skin bl ood flow. (ii) Metoprolol further reduces forearm blood now compared t o enalaprilat. (iii) Neither drug has any acute effect on insulin sens itivity. (iv) The interference of a physiological response to insulin by ACE inhibitors or beta-blocking agents may have implications both f or energy balance and thermoregulation during periods of hyperinsulina emia in man.