Acute administration of metoprolol and enalaprilat reduces insulin-stimulated thermogenesis and skin blood flow.

Author(s): Tuominen JA, Eriksson JG, Koivisto VA

Affiliation(s): Department of Medicine, Helsinki University Central Hospital, Finland.

Publication date & source: 1996-05, J Intern Med., 239(5):399-406.

Publication type: Clinical Trial; Randomized Controlled Trial

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.