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 extrarenal erythropoietin (Epo) response to hypoxia was evaluated in adult male mice with chronic renal failure from partial nephrectomy. A partial nephrectomy model for chronic renal failure was used in an attempt to evaluate erythropoiesis and Epo production in mice whose renal source of Epo may be compromised and thus more dependent on extrarenal sources. Mice with two-thirds of total renal mass excised developed a three-fold increase in serum creatinine concentration, polyuria, and polydipsia but not anemia. They responded to the combined challenge of hypobaric hypoxia (17 hours, 0.5 atm) and anemia from phenylhydrazine treatment (60 mg/kg intraperitoneally [i.p.]) with a consistent increase in serum Epo. This response was not affected by either acute or chronic bilateral submandibularectomy. However, bilateral submandibularectomy 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 submandibularectomy did not influence the extrarenal Epo response to severe hypoxia, mice with partial nephrectomies had a greater Epo response to hypoxia than control mice with a recent bilateral nephrectomy. In conclusion, the submandibular salivary glands do not appear to be an extrarenal source of Epo, nor do they appear to contribute to the enhanced extrarenal Epo response of mice with chronic renal failure.