Objective: To examine the acute effects of intravenous metoprolol and enalaprilat on energy expenditure, thermogenesis, blood flow and insulin sensitivity.
Design: Randomized, single-blind, placebo-controlled trial.
Setting: Helsinki University Central Hospital, Finland
Subjects: Seven moderately insulin-resistant nondiabetic subjects.
Interventions: Each subjects was studied three times at 2-3 week intervals: metoprolol (5 mg), enalaprilat (2 mg) or saline infusions were used.
Methods: A 150-min euglycaemic/hyperinsulinaemic clamp combined with indirect calorimetry and blood flow measurements were performed.
Main outcome measures: Glucose uptake, forearm and skin blood flow, and energy expenditure.
Results: Blood pressure was decreased to the same degree by both drugs. Forearm blood flow (plethysmography) was lower with metoprolol compared to enalaprilat (2.1 +/- 0.2 vs. 2.8 +/- 0.4 mL per 100 mL min-1; P < 0.05). Glucose-plus-insulin-stimulated thermogenesis and total energy expenditures were reduced both by metoprolol (71 and 5.2%; P < 0.05 in both) and enalaprilat (59%, P = 0.06; and 7.6%, P < 0.05) as compared to the control study. Skin blood flow (laser Doppler) increased by 100% (P < 0.01) during the glucose-plus-insulin infusion, but this increment was inhibited by both drug infusions. Forearms and whole-body glucose uptake was not influenced by metoprolol or enalaprilat administration.
Conclusions: (i) Both metoprolol and enalaprilat inhibit glucose-plus-insulin-induced thermogenesis and a rise in skin blood flow. (ii) Metoprolol further reduces forearm blood flow compared to enalaprilat. (iii) Neither drug has any acute effect on insulin sensitivity. (iv) The interference of a physiological response to insulin by ACE inhibitors or beta-blocking agents may have implications both for energy balance and thermoregulation during periods of hyperinsulinaemia in man.