Effects of oxygen breathing and erythropoietin on hypoxic vasodilation in uremic anemia

Abstract

Loss of hypoxic vasodilation has been proposed as a causative factor in the development of hypertension in dialysis patients treated with recombinant human erythropoietin (rHuEPO). Venous occlusion plethysmography was therefore performed on 22 dialysis patients (aged 23 to 71 years, dialysis duration 6 to 260 months, 8 males) before and after correction of anemia with rHuEPO, 50 U/kg 3x/week (Hb: 7.4 ± 0.3 vs. 10.8 ± 0.3 g/dl, P < 0.0001). Hypertension (> 15 mm Hg rise in mean BP) occurred in 11 patients. The study was performed while breathing room air and repeated after breathing 60% O2 for 10 to 12 minutes. Before rHuEPO therapy, total blood O2 content increased from 10.01 ± 0.39 to 10.32 ± 0.29 ml O2/100 ml blood with breathing 60% O2 (P < 0.01). After correction of anemia it was 14.65 ± 0.40 ml O2/100 ml blood on room air (P < 0.001). There was a significant decrease in forearm blood flow (7.9 ± 0.5 vs. 6.5 ± 0.6 ml/min/100 ml tissue, P < 0.05) and increase in forearm vascular resistance (12.8 ± 0.1 vs. 16.8 ± 0.2 mm Hg/ml/min/100 ml tissue, P < 0.05) with O2 breathing prior to rHuEPO therapy in the blood pressure responders, but no change in these parameters in the group in which blood pressure remained unchanged. When all patients were studied on room air, forearm vascular resistance rose significantly after correction of anemia (13.0 ± 0.8 vs. 16.3 ± 0.8 mm Hg/ml/min/100 ml tissue, P < 0.05), compared with that prior to rHuEPO therapy. However, no difference in this increase was detected between blood pressure responders and non-responders. In conclusion, forearm vascular resistance increases in uremic anemia in response to increased delivery of O2, suggesting the existence of significant hypoxic vasodilation. The reversal of hypoxic vasodilation achieved by increased pO2 is greater in patients in whom blood pressure increases during correction of anemia. The enhanced vascular reactivity to reversal of low blood oxygen content present in these patients may partly account for the development of hypertension.