INHIBITORY EFFECT OF AN ALPHA(1)-ADRENERGIC ANTAGONIST ON ERYTHROPOIESIS IN NORMOXIC OR HYPOXIC MICE

The present study was undertaken to assess the effect of prazosin, a selective postsynaptic alpha(1)-adrenergic receptor blocking agent, on normoxic and hypoxic mice, in order to evaluate experimentally its use in the treatment of the excessive erythrocytosis that characterizes chronic mountain sickness. The drug, injected intraperitoneally to adult mice at a dose of 400 mu g/kg per day, induced a significant depression of the rate or eryhtropoiesis, as measured by red blood cell (59)iron uptake, with a decrease in the hematocrit from the 3rd day. The drug also inhibited the oxygen-dependent secretion of erythropoietin (estimated by the plasma immunoreactive hormone concentration) in hypoxemic mice when injected between 0 and 2 h after initiation of the hypoxic stimulation. When injected daily into mice exposed to intermittent hypobaric hypoxia, prazosin limited the degree of polycythemia or induced a sustained decrease in the hematocrit when polycythemia was already present due to previous exposure. It is postulated that the drug, by reducing the peripheral vascular resistance seen during hypoxia, could increase renal blood flow, thus improving the renal oxygen supply and partially restoring the imbalance between gas supply and demand, which drives erythropoietin formation.