In vivo ß3-adrenergic stimulation of human thermogenesis and lipid use

S.L.H. Schiffelers, E.E. Blaak, W.H.M. Saris, M.A. van Baak

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Abstract

Objective: To investigate the role of the human Pa-adrenergic receptor in in vivo isoproterenol (INN, isoprenaline)-induced thermogenesis and lipid use. Methods: Eight male volunteers participated in two studies. In the first study subjects received oral dosages of 2.5, 7.5, 15, and 40 mg nadolol or propranolol (both beta(1)- and beta(2)-adrenergic receptor antagonists) at random, after which isoproterenol(beta(1)-, beta(2)-, and beta(3)-adrenergic receptor agonist) was infused in an individually determined dosage (range, 19 to 35 ng/kg . min) that increased energy expenditure by 25% without pretreatment. In the second study, 50, 100, and 200 ng/kg min isoproterenol or saline solution were infused after pretreatment with 80 mg nadolol. In both studies energy expenditure and respiratory exchange ratio were measured by indirect calorimetry and, at the end of each infusion period, blood samples were taken and tremor score (only first study), heart rate, and blood pressure cr ere measured. Results: In the first study, nadolol or propranolol in doses less than or equal to 40 mg could not fully block beta(1)-adrenergic receptor-mediated increases in heart rate and systolic blood pressure. Propranolol in doses less than or equal to 7.5 mg could not fully block the beta(2)-adrenergic receptor-mediated increase in tremor score during isoproterenol infusion. The increases found in thermogenesis and lipid use could therefore be explained by concomitant beta(1)- and beta(2)-adrenergic stimulation. In the second study, isoproterenol infusion induced a significant increase in heart rate, but no increases in thermogenesis and lipid use were found compared with infusion of saline solution. Conclusion: No evidence could be found for a beta(3)-adrenergic receptor-mediated increase in human thermogenesis and Lipid use during isoproterenol infusion after pretreatment with nadolol or propranolol.
Original languageEnglish
Pages (from-to)558-566
Number of pages9
JournalClinical Pharmacology & Therapeutics
Volume67
Issue number5
DOIs
Publication statusPublished - 1 Jan 2000

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