Interrelation of the renin system and erythropoietin in rats

Evidence is presented implicating the renin-angiotensin system in the regulation of plasma erythropoietin concentration. Male and female rats were exposed to hypoxia at 0.43 atm for 8 hr. In male rats, individual erythropoietin values showed a positive correlation with renin, renin substrate, and angiotensin I after 8 hr of hypoxia. In female rats, renin was not elevated during hypoxia. However, after renin was injected subcutaneously, plasma renin values became similar to those in male rats and erythropoietin doubled. Individual erythropoietin values of the combined groups showed a positive correlation with plasma renin. A single oral dose of SQ 14225, an angiotensin I-converting enzyme inhibitor, reduced erythropoietin to undetectable levels in renin-injected female rats. Angiotensin II, in subpressor amounts, prevented the suppression of erythropoietin by SQ 14225. SQ 14225 also reduced renin substrate concentration at ambient pressure and during hypoxic exposure. The correlation coefficient between renin substrate and erythropoietin in rats given SQ 14225 to lower substrate or angiotensin II to increase substrate was 0.85; p < 0.0005. The increase in renin substrate that occurred during hypoxia in female rats given angiotensin II correlated positively with erythropoietin, r = 0.86; p < 0.0005.