ERYTHROPOIETIN PRODUCTION IN HEALTHY-VOLUNTEERS SUBJECTED TO CONTROLLED HEMORRHAGE - EVIDENCE AGAINST A MAJOR ROLE FOR ADENOSINE

1 This study was carried out to assess the role of adenosine in the re gulation of human erythropoietin (EPO) production. To this end we inve stigated in healthy volunteers whether the nonspecific adenosine antag onist theophylline increases and the adenosine uptake inhibitor dipyri damole decreases EPO production in response to an haemorrhage of 750 m l. 2 Healthy male nonsmokers received i.v. in a parallel, randomized, single-blind trial theophylline (loading dose 5 mg kg(-1) over 20 min, followed by 0.5 mg kg(-1) min(-1)), dipyridamole (0.21 mg kg(-1) h(-1 )) or placebo (0.9% NaCl) for 6 h following the phlebotomy. EPO concen trations were followed up to 72 h after phlebotomy. 3 Following blood loss EPO concentrations increased during all treatments. The AUG(EPO) (0,72 h) were not statistically significantly different (theophylline: 398 +/- 30, dipyridamole: 301 +/- 15, placebo: 332 +/- 57 [mu ml(-1) h]). Creatinine clearance and urinary cAMP excretion were unaltered by any treatment. Urinary excretion of adenosine was significantly incre ased during infusion of dipyridamole. Plasma renin activitiy was signi ficantly increased during theophylline infusion. 4 In our model of con trolled, physiological stimulation of EPO production by haemorrhage, a denosine appears unlikely to play a major role as a mediator of renal EPO production.