The Role of the Renin-Angiotensin System in the Regulation of Erythropoiesis

The renin-angiotensin system is the major regulator of blood pressure by virtue of controlling vascular resistance and plasma volume. Much less recognition exists for the role of the renin-angiotensin system in regulating erythropoiesis, a biological function critical for oxygen delivery to tissues. In this review, we present evidence that angiotensin II (Ang II) is a physiologically important regulator of erythropoiesis with 2 key actions. First, Ang II is a growth factor of erythroid progenitors and, in cooperation with erythropoietin, increases red blood cell mass. Second, Ang II acts as an erythropoietin secretagogue to maintain increased erythropoietin levels despite increments in hematocrit. Among a multitude of physiologic and pathophysiologic implications, these lines of evidence provide an explanation for the effect of angiotensin-converting enzyme inhibitors and Ang II type 1 receptor blockers to decrease hematocrit or cause anemia in various clinical conditions.