THE EFFECT OF THE SUBMANDIBULAR SALIVARY-GLAND ON THE ERYTHROPOIETIN RESPONSE TO HYPOXIA IN MICE WITH CHRONIC-RENAL-FAILURE

The role of the submandibular salivary gland (SG) in the renal and ext rarenal erythropoietin (Epo) response to hypoxia was evaluated in adul t male mice with chronic renal failure from partial nephrectomy. A par tial nephrectomy model for chronic renal failure was used in an attemp t to evaluate erythropoiesis and Epo production in mice whose renal so urce of Epo may be compromised and thus more dependent on extrarenal s ources. Mice with two-thirds of total renal mass excised developed a t hree-fold increase in serum creatinine concentration, polyuria, and po lydipsia but not anemia. They responded to the combined challenge of h ypobaric hypoxia (17 hours, 0.5 atm) and anemia from phenylhydrazine t reatment (60 mg/kg intraperitoneally [i.p.]) with a consistent increas e in serum Epo. This response was not affected by either acute or chro nic bilateral submandibularectomy. However, bilateral submandibularect omy in mice with chronic renal failure was associated with a reduction in serum creatinine (p<0.01). The possibility that reduction of renal mass might increase extrarenal secretion of Epo was examined in mice with chronic renal failure by removing the kidney remnant and exposing them to a severe hypoxic challenge. While acute bilateral submandibul arectomy did not influence the extrarenal Epo response to severe hypox ia, mice with partial nephrectomies had a greater Epo response to hypo xia than control mice with a recent bilateral nephrectomy. In conclusi on, the submandibular salivary glands do not appear to be an extrarena l source of Epo, nor do they appear to contribute to the enhanced extr arenal Epo response of mice with chronic renal failure.