In vivo beta(3)-adrenergic stimulation of human thermogenesis and lipid use

Objective: To investigate the role of the human Pa-adrenergic receptor in i n vivo isoproterenol (INN, isoprenaline)-induced thermogenesis and lipid us e. Methods: Eight male volunteers participated in two studies. In the first st udy subjects received oral dosages of 2.5, 7.5, 15, and 40 mg nadolol or pr opranolol (both beta(1)- and beta(2)-adrenergic receptor antagonists) at ra ndom, 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 pret reatment. 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 sample s were taken and tremor score (only first study), heart rate, and blood pre ssure cr ere measured. Results: In the first study, nadolol or propranolol in doses less than or e qual to 40 mg could not fully block beta(1)-adrenergic receptor-mediated in creases in heart rate and systolic blood pressure. Propranolol in doses les s than or equal to 7.5 mg could not fully block the beta(2)-adrenergic rece ptor-mediated increase in tremor score during isoproterenol infusion. The i ncreases found in thermogenesis and lipid use could therefore be explained by concomitant beta(1)- and beta(2)-adrenergic stimulation. In the second s tudy, isoproterenol infusion induced a significant increase in heart rate, but no increases in thermogenesis and lipid use were found compared with in fusion of saline solution. Conclusion: No evidence could be found for a beta(3)-adrenergic receptor-me diated increase in human thermogenesis and Lipid use during isoproterenol i nfusion after pretreatment with nadolol or propranolol.