Effects of angiotensin and renal artery constriction on erythropoietin production.

The mechanism of the erythropoietic effects of angiotensin was studied in dogs and mildly plethoric mice. Renal blood flow and plasma levels of erythropoietin were measured in 20 anesthetized mongrel dogs during 6 hr of infusion with angiotensin (0.2 and 0.4 µg/ kg/min) or saline or after constriction of the renal artery with a modified Goldblatt clamp. Both dosages of angiotensin produced a decrease in renal blood flow, an increase in mean arterial pressure and a significant increase in plasma levels of erythropoietin. Renal artery constriction with the Goldblatt clamp, sufficient to reduce renal blood flow to a range of 30 to 40% of normal, also resulted in an increase in plasma erythropoietin as early as 2 hr after constriction. The erythropoietic effect of angiotensin in mildly plethoric mice was blocked by antiserum (anti-ESF) to erythropoietin. The ability of anti-erythropoietin serum to block the erythropoietic effect of angiotensin in mildly plethoric mice and the increase in plasma levels of ESF seen in dogs after angiotensin infusion indicate that the mechanism of the erythropoietic action of angiotensin is enhanced production of endogenous erythropoietin. The increased erythropoietin production seen with angiotensin is interpreted to be due to the renal hypoxia induced by the reduction in renal blood flow.