Erythropoietin production in healthy volunteers subjected to controlled haemorrhage: Evidence against a major role for adenosine

被引:17
作者
Gleiter, CH
Freudenthaler, S
Delabar, U
Eckardt, KU
Muhlbauer, B
GundertRemy, U
Osswald, H
机构
[1] UNIV TUBINGEN,INST PHARMAKOL,TUBINGEN,GERMANY
[2] HUMBOLDT UNIV BERLIN,ABT INNERE MED SCHWERPUNKT NEPHROL & INTENS MED,KLINIKUM RUDOLF VIRCHOW,BERLIN,GERMANY
关键词
erythropoietin; adenosine; theophylline; dipyridamole; haemorrhage; urinary cAMP; creatinine clearance; plasma renin activity; humans;
D O I
10.1046/j.1365-2125.1996.00484.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 This study was carried out to assess the role of adenosine in the regulation of human erythropoietin (EPO) production. To this end we investigated in healthy volunteers whether the nonspecific adenosine antagonist theophylline increases and the adenosine uptake inhibitor dipyridamole decreases EPO production in response to an haemorrhage of 750 ml. 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 concentrations 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 increased during infusion of dipyridamole. Plasma renin activitiy was significantly increased during theophylline infusion. 4 In our model of controlled, physiological stimulation of EPO production by haemorrhage, adenosine appears unlikely to play a major role as a mediator of renal EPO production.
引用
收藏
页码:729 / 735
页数:7
相关论文
共 34 条
[31]  
UZIEL M, 1976, CLIN CHEM, V22, P1451
[32]   ADRENERGIC RECEPTOR MEDIATION OF RENIN SECRETION [J].
WINER, N ;
CHOKSHI, DS ;
YOON, MS ;
FREEDMAN, AD .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1969, 29 (09) :1168-+
[33]   ERYTHROPOIESIS AND ERYTHROPOIETIN LEVELS IN RENAL-TRANSPLANT RECIPIENTS [J].
WOLFF, M ;
JELKMANN, W .
KLINISCHE WOCHENSCHRIFT, 1991, 69 (02) :53-58
[34]  
WOLFF M, 1992, PATHOPHYSIOLOGY PHAR, P99