Angiotensin II increases erythropoietin production in healthy human volunteers

Abstract

Background: A number of animal studies and our own clinical trials point towards a possible influence of the renin-angiotensin-system (RAS) on erythropoietin (EPO) production. In this study we investigated the role of angiotensin II in the regulation of EPO production in humans.

Methods: After a hemorrhage of 750 ml as a basic physiological stimulus 72 healthy male volunteers received in a parallel design either placebo (physiologic electrolyte solution) for 6 h, angiotensin II i.v. for 6 h (1-3 microgram min-1, sufficient to increase systolic blood pressure by 20 mmHg), the selective AT1-receptor antagonist losartan, the ACE-inhibitor captopril, angiotensin II + losartan, or angiotensin II + captopril.

Results: Administration of angiotensin II alone and in combination with captopril resulted in a significantly higher Cmax EPO (67% higher vs. placebo, P < 0.05) and AUCEPO (0-24h) (40% higher vs. placebo, P < 0.05). In the groups receiving losartan or captopril alone or the combination of angiotensin II + losartan no significant difference of Cmax EPO and AUCEPO(0-24h) compared to placebo could be detected.

Conclusions: This study shows in a model of controlled, basic physiological stimulation of renal EPO production that angiotensin II is able to increase EPO levels in humans. This effect of angiotensin II can be blocked by the specific AT1-receptor antagonist losartan but not by the ACE-inhibitor captopril. The result may be interpreted as a hint that one signal for the control of EPO production in humans may be mediated by angiotensin II (AT1)-receptors.