FENOTEROL BUT NOT DOBUTAMINE INCREASES ERYTHROPOIETIN PRODUCTION IN HUMANS

Objective: This study assessed the role of adrenergic signal transmiss ion 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) ei ther placebo (0.9% sodium chloride), or the beta(2)-adrenergic recepto r agonist fenoterol (1.5 mu g/min), or the beta(1)-adrenergic receptor agonist dobutamine (5 mu g/kg/min), or the nonselective beta-adrenerg ic receptor antagonist propranolol (loading dose of 0.14 mg/kg over 20 minutes, followed by 0.63 mu g/kg/min). Results: The AUC(EPO(0-48 hr) fenoterol) was 37% higher (p < 0.03) than AUC(EPO(0-48 hr)placebo), wh ereas AUC(EPO(0-48 hr)dobutamine) and AUC(EPO(0-48 hr)propranolol) wer e comparable with placebo. Creatinine clearance was significantly incr eased during dobutamine treatment. Urinary cyclic adenosine monophosph ate excretion was increased only by fenoterol treatment, whereas serum potassium levels were decreased. Plasma renin activity was significan tly increased during dobutamine and fenoterol infusion. Conclusions: T his study shows in a model of controlled, physiologic stimulation of r enal erythropoietin production that the beta(2)-adrenergic receptor ag onist fenoterol but not the beta(1)-adrenergic receptor agonist dobuta mine is able to increase erythropoietin levels in humans. The result c an be interpreted as a hint that signals for the control of erythropoi etin 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 c ausally linked to the control of erythropoietin production in this exp erimental setting.