BLOOD-PRESSURE, ERYTHROPOIETIN AND AUTONOMIC FUNCTION

The pathogenesis of hypertension induced by erythropoietin (EPO) therapy has not been completely elucidated To asses the possible implication of the autonomic nervous system in the hemodynamic response to EPO administration, we studied the autonomic function in 10 patients undergoing hemodialysis before and after 7 months receiving EPO. Assessment of autonomic function was performed using 3 tests of the parasympathetic system (Valsalva, 30/15 ratio and heart rate variation) and 3 tests of the sympathetic system (cold pressor test, amyl nitrite inhalation and orthostatic blood pressure). Cardiac and hemodynamic parameters (left ventricular mass [LVM], cardiac index [CI] and systemic vascular resistances [VR]) were assessed by M-mode and doppler echocardiography. Hormonal parameters (cathecholamines, renin activity and aldosterone) were also determined. Be fore EPO administration there was a significant difference between patients and normal subjects on parasympathetic tests (Valsalva 1.14 +/- 0.06 vs 1.64 +/- 0,09, p < 0.001; 30/15 ratio 1.10 +/- 0.03 vs 1.21 +/- 0.02, p < 0.05; heart rate variation 8.76 +/- 2.31 vs 19.80 +/- 1.99, p < 0.01) and on sympathetic tests (cold 4.27 +/- 0.87 vs 11.82 +/- 2.38, p < 0.01; amyl nitrite 5.39 +/- 1.11 vs 12.77 +/- 2.47, p < 0.01). Following correction of anemia by EPO, the VR increased (1.147 +/- 137 vs 1.276 +/- 81 din/cm/sec-5, p < 0.01) and CI fell (4.0 +/- 0.3 vs 3.4 +/- 0.2 l/min/m2, p < 0.05). Hormonal parameters and autonomic function were unaltered. In 5 patients, blood pressure did not change (non-responder group [NR]) while hypertension developed in 5 other patients (responder group [R]). After the treatment, VR increased in both groups however CI decreased only in NR (4.16 +/- 0.58 vs 3.18 +/- 0.30 l/min/m2, p < 0. 05) but not in R (3.91 +/- 0.38 vs 3.66 +/- 0.28 l/min/m2). In contrast, LVM increased in R (189 +/- 27 vs 226 +/- 36 g/m2, p < 0.05) and remained unchanged in NR. There was no difference either in autonomic tests or in hormonal parameters between those that increased their blood pressure and those that did not. These results suggest that inappropriate cardiovascular responses to correction of the anemia with EPO are not related to nervous autonomic system dysfunction.