Fenoterol but not dobutamine increases erythropoietin production in humans.
OBJECTIVE
This study assessed the role of adrenergic signal transmission in the control of renal erythropoietin (EPO) production in humans.


METHODS
Forty-six healthy male volunteers underwent a hemorrhage of 750 ml. After phlebotomy, they received (intravenously for 6 hours in a parallel, randomized, placebo-controlled and single-blind design) either placebo (0.9% sodium chloride), or the beta 2-adrenergic receptor agonist fenoterol (1.5 microgram/min), or the beta 1-adrenergic receptor agonist dobutamine (5 micrograms/kg/min), or the nonselective beta-adrenergic receptor antagonist propranolol (loading dose of 0.14 mg/kg over 20 minutes, followed by 0.63 micrograms/kg/min).


RESULTS
The AUCEPO(0-48 hr)fenoterol was 37% higher (p < 0.03) than AUCEPO(0-48 hr)placebo, whereas AUCEPO(0-48 hr)dobutamine and AUCEPO(0-48 hr)propranolol were comparable with placebo. Creatinine clearance was significantly increased during dobutamine treatment. Urinary cyclic adenosine monophosphate excretion was increased only by fenoterol treatment, whereas serum potassium levels were decreased. Plasma renin activity was significantly increased during dobutamine and fenoterol infusion.


CONCLUSIONS
This study shows in a model of controlled, physiologic stimulation of renal erythropoietin production that the beta 2-adrenergic receptor agonist fenoterol but not the beta 1-adrenergic receptor agonist dobutamine is able to increase erythropoietin levels in humans. The result can be interpreted as a hint that signals for the control of erythropoietin production may be mediated by beta 2-adrenergic receptors rather than by beta 1-adrenergic receptors. It appears to be unlikely that an increase of renin concentrations or glomerular filtration rate is causally linked to the control of erythropoietin production in this experimental setting.
Gleiter
C H
CH
Abteilung Klinische Pharmakologie, Universität Göttingen, Germany. Gleiter@med.uni-goettingen.de
Becker
T
T
Schreeb
K H
KH
Freudenthaler
S
S
Gundert-Remy
U
U
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D000242:Cyclic AMP / Q000652:urine; D004280:Dobutamine / Q000494:pharmacology*; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000096:biosynthesis* / Q000097:blood; D005280:Fenoterol / Q000494:pharmacology*; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D018962:Phlebotomy; D012083:Renin / Q000097:blood; D016037:Single-Blind Method
D000318:Adrenergic beta-Agonists; D006454:Hemoglobins; D004921:Erythropoietin; D005280:Fenoterol; D004280:Dobutamine; D000242:Cyclic AMP; D012083:Renin