Pathophysiological Roles of Renin-Angiotensin System on Erythropoietic Action

Akiyoshi      Fukamizu; Toshiro      Fujita; Hideki      Kato; Masaomi      Nangaku

Abstract

The renin-angiotensin system (RAS) has been known to exert various actions on diverse target tissues such as kidney, heart, vascular system, and brain as well as blood pressure regulation and fluid homeostasis. In addition, various animal experiments and clinical studies suggested a role of RAS on the erythropoiesis. In RAS activated clinical situations such as posttransplant erythrocytosis, renin secreting tumors, and renal artery stenosis, positive erythropoiesis has been suggested. In contrast, by use of anti-RAS drugs such as angiotensin converting enzyme inhibitors or angiotensin II type 1 receptor blockers, negative erythropoiesis has been also reported in RAS inhibited situations. In this era of genetically engineered mice available, transgenic and knockout mice of RAS components have been conspicuously analyzed and these animals definitely revealed positive and negative regulation of erythropoiesis by RAS in vivo. The primary mechanism of enhanced erythropoiesis by RAS activation is increased erythropoietin production via angiotensin II type 1 receptor. A mechanism of progression of anemia by RAS inhibition is less clear. While a slight decrease of hemoglobin is observed in association with the use anti-RAS drugs in clinical situations, other beneficial effects of these reagents apparently validate application of these reagents to patients.

Keywords: Renin-angiotensin system, erythropoiesis, genetically engineered mice, erythropoietin

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