TY - JOUR
T1 - Epinephrine and norepinephrine are cleared through beta-adrenergic, but not alpha-adrenergic, mechanisms in man
AU - Cryer, Philip E.
AU - Rizza, Robert A.
AU - Haymond, Morey W.
AU - Gerich, John E.
N1 - Funding Information:
From the Metabolism Division, Department of Medicine, Washington University School of Medicine, St. Louis, MO. and the Endocrine Research Laboratory, Mayo Clinic, Rochester, Minn. Supported in part by USPHS grants .4M 20579, RR00036. AM 2041 I. AM 20837. AM 05827, and RR00585 and by grants from the Diabetic Children’s Welfare Association/American Diabetes Association, Greater St. Louis Ajiliate andfrom the Mayo Foundation. Address reprint requests to Philip E. Cryer. M.D., Metabolism Division, Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO. 63110. 0 1980 by Grune & Stratton, Inc. 0026%0495/80/2913~003$01.00/0
PY - 1980
Y1 - 1980
N2 - Although catecholamines are rapidly removed from the extracellular fluid, the role of adrenergic mechanisms in the clearance of epinephrine and norepinephrine has not been defined. In five normal human subjects, mean (± SE) plasma epinephrine concentrations did not change during control infusions, rose from 21 ± 6 pg/ml to 834 ± 84 pg/ml during the infusion of epinephrine (50 ng/kg/min) over 180 min and to 853 ± 112 pg/ml during the infusion of epinephrine plus phentolamine (500 μg/min after a 5.0 mg loading dose infused over 2 min), but to 2400 ± 104 pg/ml during the infusion of epinephrine plus propranolol (80 μg/min after a 5.0 mg loading dose infused over 2 min), indicating that β-adrenergic blockade sharply reduces the clearance of epinephrine in man. In separate studies in seven subjects, similar increments in plasma epinephrine occurred during the infusion of epinephrine alone and the clearance of epinephrine was comparably reduced during the infusion of epinephrine plus propranolol and during the infusion of epinephrine plus propranolol plus phentolamine, suggesting that the reduction of epinephrine clearance produced by β-adrenergic blockade during epinephrine infusion is not mediated by an α-adrenergic reduction of blood flow to organs of epinephrine clearance. Endogenous plasma norepinephrine concentrations doubled during the infusion of phentolamine without propranolol but rose to nearly fourfold higher values during the infusion of phentolamine with propranolol indicating that β-adrenergic blockade reduces the clearance of norepinephrine as well as that of epinephrine. These findings indicate that epinephrine and norepinephrine are cleared through β-adrenergic, but not α-adrenergic, mechanisms in man.
AB - Although catecholamines are rapidly removed from the extracellular fluid, the role of adrenergic mechanisms in the clearance of epinephrine and norepinephrine has not been defined. In five normal human subjects, mean (± SE) plasma epinephrine concentrations did not change during control infusions, rose from 21 ± 6 pg/ml to 834 ± 84 pg/ml during the infusion of epinephrine (50 ng/kg/min) over 180 min and to 853 ± 112 pg/ml during the infusion of epinephrine plus phentolamine (500 μg/min after a 5.0 mg loading dose infused over 2 min), but to 2400 ± 104 pg/ml during the infusion of epinephrine plus propranolol (80 μg/min after a 5.0 mg loading dose infused over 2 min), indicating that β-adrenergic blockade sharply reduces the clearance of epinephrine in man. In separate studies in seven subjects, similar increments in plasma epinephrine occurred during the infusion of epinephrine alone and the clearance of epinephrine was comparably reduced during the infusion of epinephrine plus propranolol and during the infusion of epinephrine plus propranolol plus phentolamine, suggesting that the reduction of epinephrine clearance produced by β-adrenergic blockade during epinephrine infusion is not mediated by an α-adrenergic reduction of blood flow to organs of epinephrine clearance. Endogenous plasma norepinephrine concentrations doubled during the infusion of phentolamine without propranolol but rose to nearly fourfold higher values during the infusion of phentolamine with propranolol indicating that β-adrenergic blockade reduces the clearance of norepinephrine as well as that of epinephrine. These findings indicate that epinephrine and norepinephrine are cleared through β-adrenergic, but not α-adrenergic, mechanisms in man.
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U2 - 10.1016/0026-0495(80)90019-0
DO - 10.1016/0026-0495(80)90019-0
M3 - Article
C2 - 6107816
AN - SCOPUS:0019302082
SN - 0026-0495
VL - 29
SP - 1114
EP - 1118
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 11
ER -