β₂-Adrenergic stimulation of erythropoiesis in busulfan treated mice

The capability of chronic β₂-adrenoceptor activation to effectively stimulate erythrocyte production in vivo was investigated in mice which had been treated with the hematopoiesis inhibiting agent busulfan. A relatively low dose (5 mg/kg i.p.) of busulfan produced moderate depression of erythropoiesis 10 days after a single injection, as determined by ⁵⁹Fe-incorporation into erythrocytes. Administration of albuterol (1 mg/kg s.c. twice daily), a selective β₂-adrenergic agonist, significantly enhanced erythropoiesis for 5-10 days after the injection of busulfan. In a long-term study with albuterol at the same dose a significant increase in hematocrit values as well as in the circulating erythrocyte mass was found in busulfan (5 mg/kg i.p. weekly) treated mice when compared to saline-busulfan treated control mice. Simultaneous injections of the β-adrenergic blocking agent propranolol (4 mg/kg i.p.) diminished the effect of albuterol on erythropoiesis. Albuterol at a lower dose (0.1 mg/kg) had no significant effect on erythrocyte mass. In view of recent findings, which have shown that the proliferation of the pluripotent hemopoeitic stem cell pool is blocked by busulfan, it is concluded that the main site of β₂-adrenergic action on erythropoiesis is on the erythroid committed stem cell pool. In addition, enhanced release of erythropoietin from the kidney following the application of albuterol may contribute to β₂-adrenergic stimulation of erythropoiesis.