The influence of erythropoietin on levels of endothelin‐1 and nitric oxide in patients on hemodialysis

Abstract

The positive treatment effect with recombinant human erythropoietin (rhEPO) on anemia in patients with chronic renal failure is documented. However, complications such as newly originated hypertension, worsening of previous hypertension, thrombosis of arteriovenous fi stula, and hyperkalemia can be caused by the use of rhEPO. [1][2][3][4] Hypertension induced with the use of erythropoietin in therapy is a complication which affects prognosis in patients treated with dialysis. 5,6 The exact mechanism of hypertension caused by rhEPO is not yet known. The balance irregularities of local endothelin factors, such as endothelin-1 (ET-1) and nitric oxide (NO), are one of the suggested possible mechanisms included in hypertension caused by erythropoietin. [7][8][9][10][11][12][13][14][15] Endothelins are regulatory peptides, distributed in many organic systems with a strong physiological function.In 1988, Yanagisava isolated, sequenced, and cloned 21 amino acids from a fraction of unhomogenized endothelin cells and named them endothelin. 16 Yanagisava also isolated 2 isoforms of endothelin, different from the original endothelin in the second and sixth amino acid, and named them endothelin-2 and endothelin-3. These are the most powerful vasoconstrictive substances known today. [17][18][19][20][21][22] Endothelin-1 is produced in endothelin cells of blood vessels, in the heart, lungs, pancreas, spleen, kidneys, rear hypophysis, and cerebral neurons. Endothelin-1 is mostly produced in endothelin cells of blood vessels, but its concentrations are much higher in tissues than in plasma, where they are found in picomolar concentrations. The half-life of ET-1 in plasma is very short, only 60 to 90 seconds.Nitric oxide is a free gas radical included in various physiological processes such as vasodilatation, neuron transmission, immunological response, and modulation of thrombocyte function. It is synthesized from amino acid L-arginine using the enzymes of NO synthetase which convert arginine and oxygen in citrulline and NO. The relaxation of blood vessels is one of the physiological effects of NO. Nitrogen oxide has an important role in regulating the tone of blood vessels since it mediates in the vasodilatatory effect of many factors, limits the effects of vasoconstrictors, and reduces the aggregation of thrombocytes. 23 Also, higher blood speed, loss of hypoxic vasodilatation after the correction of anemia, and mobilization of vascular calcium OBJECTIVE: Examine the infl uence of the chronic use of erythropoietin on the value of endothelin-1 (ET-1) and nitric oxide (NO), as well as on ET-1/NO ratio in serum, before and after dialysis.METHODS: A total of 30 patients on hemodialysis were included in the study. Different doses of erythropoietin were administered at least 3 weeks before study. All patients had stable blood pressure values, without changes in antihypertensive therapy in the last 3 months, and without signifi cant intradialytic hypertension and hypotension. The concentration of ET-1 and NO was measured before and a...