ERYTHROPOIETIN-MEDIATED ERYTHROCYTOSIS IN RODENTS AFTER INTRA-RENAL INJECTION OF NICKEL SUBSULFIDE

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 55  (2) , 123-136
Abstract
Rats and guinea pigs developed pronounced erythrocytosis at 1-4 mo. after unilateral intrarenal (i.r.) injection of Ni3S2. At 2 mo. after i.r. administration of Ni3S2 (5 mg) to rats, blood hematocrit values averaged 70 .+-. 3% (P < 0.001, 48 .+-. 2 in controls); at 2 mo. after i.r. administration of Ni3S2 (20 mg) to guinea pigs, blood hematocrit values averaged 67 .+-. 6% (P < 0.001, 49 .+-. 1% in controls). Hamsters and gerbils did not develop erythrocytosis after i.r. injection of Ni3S2 (5 mg/animal). Administration of Ni3S2 to rats by intrasplenic injection did not increase blood hematocrit; splenectomy did not prevent erythrocytosis in rats that received i.r. injection of Ni3S2. Erythrocytosis in rats was completely blocked by excision of the Ni3S2-injected kidney but was unaffected by excision of the noninjected kidney. Partial inhibition of Ni3S2-induced erythrocytosis in rats occurred after simultaneous i.r. injection of Mn, Cu or Al dusts, benzo[a]pyrene or s.c. infusion of sodium diethyldithiocarbamate. Erythrocytosis induced by i.r. injection of Ni3S2 was augmented by i.r. injection of Cr dust or i.m. administration of Fe-dextran. Erythrocytosis occurred in rats after i.r. implantation of Ni3S2 within semipermeable cellulose tubules, indicating that phagocytosis of Ni3S2 particles was not necessary for erythropoietic stimulation. Erythropoietin (Ep) activity in rat serum increased 6-fold at 2 wk after i.r. injection of Ni3S2 (P < 0.001, controls), but Ep activity in pooled extracts of Ni3S2-treated rat kidneys did not increase significantly. This study identified several factors that influenced erythropoietic stimulation by Ni3S2, and furnished salient information concerning the pathogenesis of Ni3S2-induced erythrocytosis.