Cardiovascular effects of erythropoietin and anemia correction.
Although recombinant erythropoietin has no short-acting pressor effect in vivo, its long-term administration frequently raises arterial pressure in humans and animals, with renal insufficiency. Contrary to the original view, erythropoietin-induced hypertension is not due to amelioration of anemia, because a similar rise in blood pressure occurs, despite persistent anemia, in erythropoietin-treated iron-deficient animals and humans. Moreover, multiple small blood transfusions administered to simulate the action of erythropoietin fail to increase blood pressure. Finally, iron repletion in severely anemic iron-deficient patients maintained on constant erythropoietin dosages does not raise blood pressure, despite a dramatic increase in hematocrit. Thus, chronic erythropoietin administration results in a hematocrit-independent, vasoconstriction-dependent hypertension that is marked by, and largely due to, elevated resting and agonist-stimulated cytoplasmic calcium concentration, leading to resistance to the vasodilatory action of nitric oxide. In addition, increased endothelin production, upregulation of tissue (but not circulating) renin and angiotensinogen expression, and a possible change in vascular tissue prostaglandin production have been variably demonstrated with erythropoietin administration in humans, intact animals and cultured endothelial cells. Erythropoietin has been shown to promote angiogenesis and stimulate endothelial and vascular smooth muscle cell proliferation. Finally, partial correction of anemia with erythropoietin therapy may partly prevent or reverse left ventricular hypertrophy in dialysis-dependent and dialysis-independent patients with chronic renal insufficiency. However, data on the risks and benefits of complete correction of anemia in this population are limited and inconclusive, and await future investigation.
Vaziri
N D
ND
Division of Nephrology and Hypertension, Departments of Medicine, University of California, Irvine, California, USA. ndvaziri@uci.edu
D000740:Anemia / Q000188:drug therapy* / Q000503:physiopathology*; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D004921:Erythropoietin / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced*; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D004921:Erythropoietin