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The effect of renal erythropoietin on nitric oxide levels in patients with chronic renal failure

Yıl 2013, Cilt 20, Sayı 2, 43 - 47, 30.06.2013

Öz

Nitric oxide (NO) is a strong vasoactive substance which contributes to the regulation of blood pressure. One of the most frequently complications seen during haemodialysis (HD) in patients with chronic renal failure (CRF) is hypertension. It was could not explain clearly that endogen production of NO increases or decreases in this patients. Moreover, CRF causes anemia via decreasing production of renal erythropoietin (EPO). EPO is used for the treatment of anemia caused by CRF. Although the mechanism of effect of EPO is not known, it is known that it increase blood pressure. For this reason, it is planned in this study that the changes in NO levels caused by EPO in patients with CRF taking and not taking EPO. Patients with CRF (n= 17) and mean age was 45 16 year to whom HD was applied in HD unit of Isparta Government Hospital were included in this study. Systolic blood pressure and serum NO levels were determined at the beginning 0 th minute (min.), 60th min., 120th min., 180th min. and at the end of the HD (240th min.). NO levels were determined by using spectrofotometric method. Statistically, significant decrease in NO levels was found at 180th and 240th min. of HD in EPO taking patients according to not taking patients with CRF(p<0.05). In conclusion; It is suggested that hypertension caused by EPO during HD may results from decreased serum NO levels.

Kaynakça

  • Furchgott, RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;288:373–376.
  • Feelisch, M, te Poel M, Zamora R, Deussen A, Moncada S. Understanding the controversy over t h e i d e n t i t y o f E D R F . N a t u r e 1994;368(6466):62–65.
  • Palmer, RMJ, Moncada S. A novel citrulline- forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem Biophys Res Commun 1989;158:348-352.
  • Bredt, DS, Snyder SH. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc Nall Acad Sci USA 1990;87:682-685.
  • Moncada, S, Higgs EA. Endogenous nitric oxide: physiology, pathology and clinical relevance. Eur J Clin Invest 1991;21(4):361–374.
  • Kim, KE, Neff M, Cohen B, Somerstein M, Chinitz J, Onesti G et al. Blood volume changes and hypotension during hemodialysis. Trans Am Soc Artif Intern Organs 1970; 16:508-514.
  • Rysz, J, Luciak M, Kedziora J, Blaszczyk J, Sibinska E. Nitric oxide release in the peripheral blood during hemodialysis. Kidney Int 1997;51:294–300.
  • Yokokawa, K, Mankus R, Saklayen MG, Kohno M, Yasunari K, Minami M et al. Increased Nitric Oxide Production in Patients with Hypotension during Hemodialysis Annals of Internal Medicine 1995;123(1):35-37
  • Shultz, PJ, Tolins JP. Adaptation to Increased Dietary Salt Intake in the Rat Role of Endogenous Nitric Oxide. The Journal of Clinical Investigation 1993;91:642-650.
  • Marletta MA, Yoon PS, Lyengar R, Leaf CD, Wishnok JS. Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry 1988;27: 8706-8711.
  • Abraham PA, Macres MG. Blood pressure in hemodialysis patients during amelioration of anemia with erythropoietin. J Am Soc Nephrol 1991;2:927–936.
  • Buckner FS, Eschbach JW, Haley NR, Davidson RC, Adamson JW. Hypertension following erythropoietin therapy in anemic hemodialysis patients. Am J Hypertens 1990;3:947–955.
  • Raine AEG, Roger SD. Effects of erythropoietin on BP. Am J Kidney Dis 1991;18:76–83.
  • Raine, AEG. Hypertension, blood viscosity and cardiovascular morbidity in renal failure: implications of erythropoietin therapy. Lancet 1988;1:97–99.
  • Steffen HM, Brunner R, Muller R, Dengenhardt S, Pollok M, Lang R et al. Peripheral hemodynamics, blood viscosity, and the renin- angiotensin system in hemodialysis patients under therapy with recombinant human erythropoietin. Contrib Nephrol 1989;76:292–298.
  • Neff MS, Kim KE, Persoff M, Onesti G, Swartz C. Hemodynamics of uremic anemia. Circulation 1971;43:876–883.
  • Martin J, Moncada S. Blood pressure, erythropoietin and nitric oxide. Lancet 1988;1:644. Letter.
  • Carlini R, Obialo CI, Rothstein M. Intravenous erythropoietin (rHuEPO) administration increases plasma endothelin and blood pressure in hemodialysis patients. Am J Hypertens 1993;6:103–107.
  • Eggena, P, Willsey P, Jamgotchian N, Truckenbrod L, Hu MS, Barrett JD et al. Influence of recombinant human erythropoietin on blood pressure and renin-angiotensin systems. Am J Physiol 1991;261:E642–E646.
  • Heidenreich, S, Rahn KH, Zidek W. Direct vasopressor effect of recombinant human erythropoietin on renal resistance vessels. Kidney Int 1999;39:259 –265.
  • Baylis, C, Vallance P. Measurement of nitrite, and nitrate (NOx) levels in plasma and urine; what does this measure tell us about the activity of the endogenous nitric oxide. Curr Opin Nephrol Hypertens 1998;7:1–4.
  • Muntzel, M, Hannedouche T, Lacour B, Drueke T. Effect of erythropoietin on hematocrit and blood pressure in normotensive and hypertensive rats. J Am Soc Nephrol 1992;3: 182–187.
  • Wilcox, CS, Deng X, Doll AH, Snellen H, Welch WJ. Nitric oxide mediates renal vasodilation during erythropoietin-induced polycythemia. Kidney Int 1993;44:430–435.
  • Vaziri, ND, Zhou M, Smith J, Oveisi F, Baldwin K, Purdy RD. In vivo and in vitro pressor effects of erythropoietin in rats. Am J Physiol 1995;269: F838–F845.
  • Kitamura M., Saito A.: Dialysis hypotension: a rewiew of recent studies of causative factors; Nephrology 2001;6(3):109-112
  • Schreiber M.J. Clinical dilemmas in dialysis: Managing the hypotensive patient setting the stage; Am J Kidney Dis 2001;38(4),4:1-10.
  • Perazella MA. Pharmacologic options available to treat symptomatic intradialytic hypotension; Am J Kidney Dis 2001;38(4),4:26-36.
  • Eschbach J.W.The Anemia of Chronic Renal Failure:Pathophysiology and the Effects of Recombinant Erytropoietin Kidney Int 1989;35:134-148.
  • Faulds D., Sorkin E.M; r-HuEPO(Recombinant Human Erythropoietin Review of its Pharmacodynamic and Pharmacokinetic properties and Therapeutic Potential in Anemia and the Stimulation of Erythropoiesis Drugs 1989;6:863- 899.
  • Aiello S, Noris M, Todeschini M, Zappella S, Foglieni C, Benigni A et al. Renal and systemic nitric oxide synthesis in rats with renal mass reduction. Kidney Int 1997;52:171–181.
  • Vaziri ND, Ni Z, Wang XQ, Oveisi F, Zhou XJ. Down-regulation of nitric oxide synthase in chronic renal insufficiency: role of excess PTH. Am J Physiol 1998;274(Renal Physiol.):642– 649.
  • MacAllister RJ, Whitley GS, Vallance P. Effects of guanidino and uremic compounds on nitric oxide pathways. Kidney Int 1994;45:737–742.
  • Casati S, Passerini P, Campise MR et al. Benefits and risks of protracted treatment with human recombinant erythropoietin in patients having hemodialysis. Br Med J 1987; 295:1017-1020.
  • Eschbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW. Correction of the anemia of end-stage renal disease with recombinant human erythropoietin: results of a combined phase I and II clinical trial. N Engl Med J 1987;316:73-78.
  • Blumberg A, Nelp WD, Hegstrom RM, Scribner BH: Extracellular volume in patients with chronic renal disease treated for hypertension by sodium restriction. Lancet 1967;2:69-73.
  • Altýntepe L, Tonbul HZ, Mil S, Türk S, Yeksan M. Hemodializ Hastalarýnda Hipertansiyon Sýklýðý ve Volüm Kontrolünün Önemi. Türk Nefroloji Diyaliz ve Transplantasyon Dergisi /Official Journal of the Turkish Society of Nephrology 2002;ll(l):32-35

KRONİK BÖBREK YETMEZLİKLİ HASTALARDA RENAL ERİTROPOİETİNİN NİTRİK OKSİD DÜZEYLERİNE ETKİSİ

Yıl 2013, Cilt 20, Sayı 2, 43 - 47, 30.06.2013

Öz

Nitrik oksid (NO) kan basıncının düzenlenmesinde önemli katkıları olan güçlü bir vazoaktif maddedir. Kronik böbrek yetmezliği (KBY) nedeniyle hemodiyaliz (HD) uygulanan hastalarda en sık görülen komplikasyonlardan birisi HD sırasında meydana gelen hipotansiyondur. Bu hastalarda endojen NO üretiminin arttığı veya azaldığı yönündeki bilgiler tam olarak açıklanamamıştır. Ayrıca KBY, böbrek eritropoietin (EPO) üretimini azaltarak anemiye neden olur. EPO, KBY anemisinin tedavisinde kullanılmaktadır. EPO'nun mekanizması tam bilinmemekle birlikte kan basıncını yükselttiği bilinmektedir. Bu nedenle çalışmamızda EPO alan ve almayan KBY hasta gruplarında, EPO'nun NO düzeylerinde meydana getirdiği değişikliklerin araştırılması planlanmıştır. Çalışmayı Isparta Devlet Hastanesi HD ünitesinde HD uygulanan yaş ortalaması 45+/-16 olan 17 KBY hastası oluşturmuştur. Olgulardan HD başlangıcı 0. Dakika (Dk.), 60. Dk. 120. Dk. ve HD sonunda (240. Dk), sistolik kan basınçları ve serum NO düzeyleri ölçülmüştür. HD uygulanan ve EPO alan KBY hastalarında, EPO almayanlara göre HD'in 180. Dk. ve 240. Dk'sında serum NO düzeylerinde istatistiksel olarak anlamlı bir düşüş saptanmıştır (p<0.05). Sonuç olarak HD sırasında EPO'nun hipertansiyona neden olduğu azalmış olan serum NO düzeylerinin katkıda bulunabileceği kanaatine varılmıştır.

Kaynakça

  • Furchgott, RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;288:373–376.
  • Feelisch, M, te Poel M, Zamora R, Deussen A, Moncada S. Understanding the controversy over t h e i d e n t i t y o f E D R F . N a t u r e 1994;368(6466):62–65.
  • Palmer, RMJ, Moncada S. A novel citrulline- forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem Biophys Res Commun 1989;158:348-352.
  • Bredt, DS, Snyder SH. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc Nall Acad Sci USA 1990;87:682-685.
  • Moncada, S, Higgs EA. Endogenous nitric oxide: physiology, pathology and clinical relevance. Eur J Clin Invest 1991;21(4):361–374.
  • Kim, KE, Neff M, Cohen B, Somerstein M, Chinitz J, Onesti G et al. Blood volume changes and hypotension during hemodialysis. Trans Am Soc Artif Intern Organs 1970; 16:508-514.
  • Rysz, J, Luciak M, Kedziora J, Blaszczyk J, Sibinska E. Nitric oxide release in the peripheral blood during hemodialysis. Kidney Int 1997;51:294–300.
  • Yokokawa, K, Mankus R, Saklayen MG, Kohno M, Yasunari K, Minami M et al. Increased Nitric Oxide Production in Patients with Hypotension during Hemodialysis Annals of Internal Medicine 1995;123(1):35-37
  • Shultz, PJ, Tolins JP. Adaptation to Increased Dietary Salt Intake in the Rat Role of Endogenous Nitric Oxide. The Journal of Clinical Investigation 1993;91:642-650.
  • Marletta MA, Yoon PS, Lyengar R, Leaf CD, Wishnok JS. Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry 1988;27: 8706-8711.
  • Abraham PA, Macres MG. Blood pressure in hemodialysis patients during amelioration of anemia with erythropoietin. J Am Soc Nephrol 1991;2:927–936.
  • Buckner FS, Eschbach JW, Haley NR, Davidson RC, Adamson JW. Hypertension following erythropoietin therapy in anemic hemodialysis patients. Am J Hypertens 1990;3:947–955.
  • Raine AEG, Roger SD. Effects of erythropoietin on BP. Am J Kidney Dis 1991;18:76–83.
  • Raine, AEG. Hypertension, blood viscosity and cardiovascular morbidity in renal failure: implications of erythropoietin therapy. Lancet 1988;1:97–99.
  • Steffen HM, Brunner R, Muller R, Dengenhardt S, Pollok M, Lang R et al. Peripheral hemodynamics, blood viscosity, and the renin- angiotensin system in hemodialysis patients under therapy with recombinant human erythropoietin. Contrib Nephrol 1989;76:292–298.
  • Neff MS, Kim KE, Persoff M, Onesti G, Swartz C. Hemodynamics of uremic anemia. Circulation 1971;43:876–883.
  • Martin J, Moncada S. Blood pressure, erythropoietin and nitric oxide. Lancet 1988;1:644. Letter.
  • Carlini R, Obialo CI, Rothstein M. Intravenous erythropoietin (rHuEPO) administration increases plasma endothelin and blood pressure in hemodialysis patients. Am J Hypertens 1993;6:103–107.
  • Eggena, P, Willsey P, Jamgotchian N, Truckenbrod L, Hu MS, Barrett JD et al. Influence of recombinant human erythropoietin on blood pressure and renin-angiotensin systems. Am J Physiol 1991;261:E642–E646.
  • Heidenreich, S, Rahn KH, Zidek W. Direct vasopressor effect of recombinant human erythropoietin on renal resistance vessels. Kidney Int 1999;39:259 –265.
  • Baylis, C, Vallance P. Measurement of nitrite, and nitrate (NOx) levels in plasma and urine; what does this measure tell us about the activity of the endogenous nitric oxide. Curr Opin Nephrol Hypertens 1998;7:1–4.
  • Muntzel, M, Hannedouche T, Lacour B, Drueke T. Effect of erythropoietin on hematocrit and blood pressure in normotensive and hypertensive rats. J Am Soc Nephrol 1992;3: 182–187.
  • Wilcox, CS, Deng X, Doll AH, Snellen H, Welch WJ. Nitric oxide mediates renal vasodilation during erythropoietin-induced polycythemia. Kidney Int 1993;44:430–435.
  • Vaziri, ND, Zhou M, Smith J, Oveisi F, Baldwin K, Purdy RD. In vivo and in vitro pressor effects of erythropoietin in rats. Am J Physiol 1995;269: F838–F845.
  • Kitamura M., Saito A.: Dialysis hypotension: a rewiew of recent studies of causative factors; Nephrology 2001;6(3):109-112
  • Schreiber M.J. Clinical dilemmas in dialysis: Managing the hypotensive patient setting the stage; Am J Kidney Dis 2001;38(4),4:1-10.
  • Perazella MA. Pharmacologic options available to treat symptomatic intradialytic hypotension; Am J Kidney Dis 2001;38(4),4:26-36.
  • Eschbach J.W.The Anemia of Chronic Renal Failure:Pathophysiology and the Effects of Recombinant Erytropoietin Kidney Int 1989;35:134-148.
  • Faulds D., Sorkin E.M; r-HuEPO(Recombinant Human Erythropoietin Review of its Pharmacodynamic and Pharmacokinetic properties and Therapeutic Potential in Anemia and the Stimulation of Erythropoiesis Drugs 1989;6:863- 899.
  • Aiello S, Noris M, Todeschini M, Zappella S, Foglieni C, Benigni A et al. Renal and systemic nitric oxide synthesis in rats with renal mass reduction. Kidney Int 1997;52:171–181.
  • Vaziri ND, Ni Z, Wang XQ, Oveisi F, Zhou XJ. Down-regulation of nitric oxide synthase in chronic renal insufficiency: role of excess PTH. Am J Physiol 1998;274(Renal Physiol.):642– 649.
  • MacAllister RJ, Whitley GS, Vallance P. Effects of guanidino and uremic compounds on nitric oxide pathways. Kidney Int 1994;45:737–742.
  • Casati S, Passerini P, Campise MR et al. Benefits and risks of protracted treatment with human recombinant erythropoietin in patients having hemodialysis. Br Med J 1987; 295:1017-1020.
  • Eschbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW. Correction of the anemia of end-stage renal disease with recombinant human erythropoietin: results of a combined phase I and II clinical trial. N Engl Med J 1987;316:73-78.
  • Blumberg A, Nelp WD, Hegstrom RM, Scribner BH: Extracellular volume in patients with chronic renal disease treated for hypertension by sodium restriction. Lancet 1967;2:69-73.
  • Altýntepe L, Tonbul HZ, Mil S, Türk S, Yeksan M. Hemodializ Hastalarýnda Hipertansiyon Sýklýðý ve Volüm Kontrolünün Önemi. Türk Nefroloji Diyaliz ve Transplantasyon Dergisi /Official Journal of the Turkish Society of Nephrology 2002;ll(l):32-35

Ayrıntılar

Birincil Dil Türkçe
Konular Diş Hekimliği
Bölüm Araştırma Makaleleri
Yazarlar

Mehmet AKDOĞAN>


Mehmet SEZER>


Emin ŞAVİK>


Duygu DOĞUÇ>

Yayımlanma Tarihi 30 Haziran 2013
Gönderilme Tarihi 4 Mayıs 2012
Kabul Tarihi
Yayınlandığı Sayı Yıl 2013, Cilt 20, Sayı 2

Kaynak Göster

Vancouver Akdoğan M. , Sezer M. , Şavik E. , Doğuç D. KRONİK BÖBREK YETMEZLİKLİ HASTALARDA RENAL ERİTROPOİETİNİN NİTRİK OKSİD DÜZEYLERİNE ETKİSİ. SDÜ Tıp Fakültesi Dergisi. 2013; 20(2): 43-47.

14791


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