The serum erythropoietin levels of adult male and female rats exposed immediately after nephrectomy to a simulated altitude of 22,000 ft for 5 hr is measurable but decreased to about l5% of normal. Erythropoietin is not detected in the serum of adult female and male rats when the interval between nephrectomy and the beginning of the hypoxic exposure is increased to 8 and 16 rr, respectively. The ability of an anephric rat to respond to this hypoxic stimulus progressively decreases with increasing time after nephrectomy. The ability of young anephric rats to increase their serum erythropoietin levels is little altered if the rats are exposed to hypoxia immediately after nephrectomy, but exposure to the same hypoxic stimulus 24 hr later results in a significant reduction in erythropoietin production. The ability of both normal and anephric rats to produce erythropoietin is reduced or abolished by actinomycin D. The serum erythropoietin produced in hypoxic anephric rats is immunologically indistinguishable from normal erythropoietin.

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