Increased Activity of the Autonomic Nervous System and Increased Sensitivity to Angiotensin II Infusion after Therapy with Recombinant Human Erythropoietin

Bernhard Heintz, MD, Department of Internal Medicine II, RWTH Aachen, Pauwelsstreet 30, D-5100 Aachen (FRG) Dear Sir, The pathophysiological role of the autonomic nervous system in the development of arterial hypertension during regular therapy with recombinant human erythropoietin (rh-EPO) is unclear [1]. Recently, Fritschka et al. [2] reported elevated plasma norepinephrine concentrations and a decrease of < 3⁄4-adrenoreceptors in dialysis patients treated with rh-EPO. Blood samples were drawn from 11 haemodialysis patients at rest and at the peak of physical exercise (initially 25 W, increased by 25 W every 2 min) to determine epinephrine (E), norepinephrine (NE), aldosterone (ALD) concentrations and plasma renin activity (PRA) before and after 6 weeks and 3 months of rh-EPO treatment. An initial dose of 40 IU/kg body weight 3 times per week intravenously was administered. If a haematocrit of 35% was not reached after 4 weeks the dose was increased by 40 IU/kg body weight. If the haematocrit exceeded 35% the dose was reduced by 40 IU/kg body weight or the infusion was completely stopped. Before, after 6 weeks and 3 months after rh-EPO administration an angiotensin II infusion test was performed (initial dose 0.5 μg/min with stepwise increase of 0.5 μg/min until the mean arterial pressure showed an increase of 20 mm Hg). Cardiac output (technetium ven-triculography) was measured and total peripheral resistance (TPR) calculated from mean arterial blood pressure as well (table 1). Resting blood pressure values did not change during the course of rh-EPO therapy. Aldosterone and renin activity also remained unchanged, but epinephrine and particularly norepinephrine increased during rh-EPO therapy, with a peak at 6 weeks of treatment. Exercise caused the systolic blood pressure to increase before and