Abstract
To determine the plasma epinephrine thresholds for its metabolic and hemodynamic actions and plasma epinephrine metabolic clearance rates, 60-min intravenous epinephrine infusions at nominal rates of 0.1, 0.5, 1.0, 2.5, and 5.0 microgram/min were performed in each of six normal human subjects. These 30 infusions resulted in steady-state plasma epinephrine concentrations ranging from 24 to 1,020 pg/ml. Plasma epinephrine thresholds were 50-100 pg/ml for increments in heart rate, 75-125 pg/ml for increments in blood glycerol and systolic blood pressure, 150-200 pg/ml for increments in plasma glucose (the resultant of increments in glucose production and decrements in glucose clearance), blood lactate, blood beta-hydroxybutyrate, and diastolic blood pressure, and greater than 400 pg/ml for early decrements in plasma insulin. Changes in blood alanine, plasma glucagon, plasma growth hormone, and plasma cortisol were not detected. At steady-state plasma epinephrine concentrations of 24-74 pg/ml, values overlapping the basal normal range, the mean (+/-SE) plasma metabolic clearance rate of epinephrine was 52 +/- 4 ml x min-1 x kg-1; this value rose to 89 +/- 6 ml x min-1 x kg-1 (P less than 0.01) at steady-state epinephrine concentrations of 90-1,020 pg/ml. We conclude that in human subjects: (a) the plasma epinephrine thresholds for its hemodynamic and metabolic actions lie within the physiologic range, (b) epinephrine and norepinephrine accelerate their own metabolic clearance, and (c) epinephrine is 10 times more potent than norepinephrine.
MeSH Terms
Adult
Blood Glucose/metabolism
Blood Pressure/drug effects
Dose-Response Relationship, Drug
Epinephrine/blood,pharmacology
Female
Glucagon/blood
Heart Rate/drug effects
Humans
Insulin/blood
Kinetics
Male
Metabolic Clearance Rate
Norepinephrine/blood
Chemicals
Blood Glucose
Insulin
Glucagon
Norepinephrine
Epinephrine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Clutter W E
Bier D M
Shah S D
Cryer P E
References (29)
29 references, click to expand
-
Hormone-fuel interrelationships during fasting.
J Clin Invest. 1966 Nov;45(11):1751-69
PMID: 5926444
-
Enzymic assay of glycerol, dihydroxyacetone, and glyceraldehyde.
Arch Biochem Biophys. 1967 Aug;121(2):404-14
PMID: 6057108
-
Comparison of competitive protein binding radioassay of cortisol to double isotope dilution and Porter Silber methods.
Steroids. 1970 Jun;15(6):765-76
PMID: 4913930
-
Glucoregulatory responses in normal and diabetic dogs recorded by a new tracer method.
Metabolism. 1971 Apr;20(4):360-72
PMID: 5550303
-
A microfluorometric enzymatic assay for the determination of alanine and pyruvate in plasma and tissues.
J Lab Clin Med. 1972 Sep;80(3):434-41
PMID: 4403429
-
A simplified radiometric assay for plasma norepinephrine and epinephrine.
Anal Biochem. 1973 Feb;51(2):618-31
PMID: 4349454
-
Plasma norepinephrine and epinephrine in untreated diabetics, during fasting and after insulin administration.
Diabetes. 1974 Jan;23(1):1-8
PMID: 4203518
-
Stimulation of glucagon secretion by epinephrine in man.
J Clin Endocrinol Metab. 1973 Sep;37(3):479-81
PMID: 4785433
-
A two-compartment calculator for the dog glucose pool in the nonsteady state.
Fed Proc. 1974 Jul;33(7):1869-76
PMID: 4834191
-
Measurement of norepinephrine and epinephrine in small volumes of human plasma by a single isotope derivative method: response to the upright posture.
J Clin Endocrinol Metab. 1974 Dec;39(6):1025-9
PMID: 4473459
-
Glucagon and plasma catecholamine responses to graded and prolonged exercise in man.
J Appl Physiol. 1975 Jan;38(1):70-6
PMID: 1110246
-
Uncontrolled diabetes mellitus and hyperglucagonemia associated with an islet cell carcinoma.
Am J Med. 1975 Feb;58(2):285-93
PMID: 46704
-
The role of adrenergic mechanisms in the substrate and hormonal response to insulin-induced hypoglycemia in man.
J Clin Invest. 1976 Jul;58(1):7-15
PMID: 6491
-
Norepinephrine and epinephrine release and adrenergic mediation of smoking-associated hemodynamic and metabolic events.
N Engl J Med. 1976 Sep 9;295(11):573-7
PMID: 950972
-
Plasma catecholamine levels in the coronary sinus, aorta and femoral vein of subjects undergoing cardiac catheterization at rest and during exercise.
Jpn Circ J. 1976 Aug;40(8):929-34
PMID: 966374
-
Isotope-derivative measurements of plasma norepinephrine and epinephrine in man.
Diabetes. 1976 Nov;25(11):1071-82
PMID: 825406
-
In-vivo measurement of glucose and alanine metabolism with stable isotopic tracers.
Diabetes. 1977 Nov;26(11):1005-15
PMID: 334614
-
Measurement of "true" glucose production rates in infancy and childhood with 6,6-dideuteroglucose.
Diabetes. 1977 Nov;26(11):1016-23
PMID: 913891
-
Catecholamines and intermediary metabolism.
Clin Endocrinol Metab. 1977 Nov;6(3):599-631
PMID: 338215
-
Catecholamines and the regulation of hormone secretion.
Clin Endocrinol Metab. 1977 Nov;6(3):657-95
PMID: 338216
-
Experimental validation of measurements of glucose turnover in nonsteady state.
Am J Physiol. 1978 Jan;234(1):E84-93
PMID: 623255
-
Norepinephrine: hormone and neurotransmitter in man.
Am J Physiol. 1978 Mar;234(3):E252-6
PMID: 24347
-
Plasma catecholamines in diabetes. The syndromes of hypoadrenergic and hyperadrenergic postural hypotension.
Am J Med. 1978 Mar;64(3):407-16
PMID: 637056
-
Relationship between the plasma glucose level and glucose uptake in the conscious dog.
Metabolism. 1978 Jul;27(7):787-91
PMID: 661564
-
Differential effects of epinephrine on glucose production and disposal in man.
Am J Physiol. 1979 Oct;237(4):E356-62
PMID: 495714
-
Determination of norepinephrine apparent release rate and clearance in humans.
Life Sci. 1979 Oct 22;25(17):1461-70
PMID: 513964
-
EFFECT OF ISCHEMIA ON KNOWN SUBSTRATES AND COFACTORS OF THE GLYCOLYTIC PATHWAY IN BRAIN.
J Biol Chem. 1964 Jan;239:18-30
PMID: 14114842
-
A SENSITIVE DOUBLE ANTIBODY IMMUNOASSAY FOR HUMAN GROWTH HORMONE IN PLASMA.
Nature. 1964 Sep 12;203:1141-2
PMID: 14213659
-
Studies on the mechanism of epinephrine-induced hyperglycemia in man. Evidence for participation of pancreatic glucagon secretion.
Diabetes. 1976 Jan;25(1):65-71
PMID: 1107095