Peripheral Hemodynamics, Blood Viscosity, and the Renin-Angiotensin System in Hemodialysis Patients under Therapy with Recombinant Human Erythropoietin

Steffen, H. M.; Brunner, Ralf; Müller, Roman‐Ulrich; Degenhardt, S.; Pollok, M.; Lang, R.; Baldamus, C. A.

doi:10.1159/000417905

Cited by 41 publications

(15 citation statements)

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“…On this concept a suppression of RAS should be expected after administra tion of rhEPO. However, both suppression [II, 13,28] or no change of PRA [12,29] and recently even an increase in renin-specific mRNA in kidney tissue [30] were found. Inconsistency of these data can be explained by the fact that various parts of the proposed feedback loop were analyzed separately in both clinical and experimental studies.…”

Section: Discussionmentioning

confidence: 99%

Influence of the Renin-Angiotensin System Stimulation on Erythropoietin Production in Patients with Various Forms of Arterial Hypertension

Nowicki¹,

Kokot²,

Wiȩcek³

1993

Nephron

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Recent studies suggest the existence of a relationship between the renin-angiotensin system and erythropoietin (EPO) secretion. It has been studied whether patients with various forms of arterial hypertension (essential, renal, renovascular, in the course of arteritis) differ with respect to EPO secretion and whether EPO serum levels are related to renin response induced by dietary sodium restriction to 10-20 mmol Na/24 h for 3 days and upright body position for 3 h. Patients with different forms of hypertension and normal renal excretory function and healthy subjects did not differ in hematocrit value, markers of iron metabolism, and EPO secretion except for patients with arteritis who had higher ferritin values. In these patients a positive correlation between EPO levels and hematocrit values suggests the existence of an altered regulation of EPO secretion. In essential hypertension a negative correlation found between changes in EPO and PRA levels in response to sodium restriction and upright body position may also reflect an altered regulation of both EPO and renin production.

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Section: Discussionmentioning

confidence: 99%

Influence of the Renin-Angiotensin System Stimulation on Erythropoietin Production in Patients with Various Forms of Arterial Hypertension

Nowicki¹,

Kokot²,

Wiȩcek³

1993

Nephron

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“…Early studies recognized that increased blood viscosity as a result of rising hematocrit values contributed to high blood pressure during chronic treatment with EPO [248]. The correction of anemia by EPO resulted in an increase in erythrocyte mass and blood viscosity [249] and the reversal of hypoxic vasodilation in uremic anemia [250]. Further studies demonstrated that constant dosage and chronic administration of EPO in iron-deficient renal anemic patients did not increase blood pressure despite a dramatic increase in hematocrit by iron repletion [251].…”

Section: Epo and Its Future For Clinical Medicinementioning

confidence: 99%

Erythropoietin on a Tightrope: Balancing Neuronal and Vascular Protection between Intrinsic and Extrinsic Pathways

Chong

Maiese³

2004

Neurosignals

102

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Enthusiasm for erythropoietin (EPO) as a broad cytoprotective agent continues to increase at an almost exponential rate. The premise that EPO was required only for erythropoiesis was eventually shed by recent work demonstrating the existence of EPO and its receptor in other organs and tissues outside of the liver and the kidney, such as the brain and heart. As a result, EPO has been identified as a possible candidate in the formulation of therapeutic strategies for both cardiac and nervous system diseases. EPO has been shown to mediate an array of vital cellular functions that involve progenitor stem cell development, cellular protection, angiogenesis, DNA repair, and cellular longevity. An important requirement to achieve the goal of preventing or even reducing cellular injury by any cytoprotective agent is the ability to uncover the cellular pathways that ultimately drive a cell to its demise. We present for consideration several critical cellular pathways modulated by EPO that involve Janus kinase 2 (Jak2), the serine-threonine kinase Akt, forkhead transcription factors, glycogen synthase kinase-3β (GSK-3β), cellular calcium, protein kinase C, caspases, as well as the control of inflammatory microglial activation. As we continue to gain new insight into these pathways, EPO should emerge as a critical agent for the development, maturation, and survival of cells throughout the body.

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“…Chief among them is the resulting rise in hematocrit, which is thought to raise vascular resistance by increase in blood viscosity, loss of hypoxic vasodilation, and enhanced competition by hemoglobin for endothelium-derived nitric oxide (NO). [4][5][6][7] Other proposed mechanisms include volume expansion, increased endothelin production, 8 enhanced tissue renin-angiotensin activity, 9 and direct vasopressor action of EPO. 10 In a series of recent studies, we demonstrated that EPOinduced hypertension is not due to the associated increase in hematocrit or erythrocyte mass.…”

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confidence: 99%

Nitric Oxide Metabolism in Erythropoietin-Induced Hypertension

Wang

Vaziri

1998

Hypertension

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Abstract-Long-term administration of erythropoietin (EPO) frequently causes hypertension in humans and animals with chronic renal failure (CRF). We recently demonstrated that EPO-induced hypertension is hematocrit independent and accompanied by elevated cytosolic [Ca 2ϩ ] i and nitric oxide (NO) resistance. This study was undertaken to examine the effects of therapy with EPO alone or together with calcium channel blockade on NO metabolism. Urinary excretion of NO metabolites (NOx) and thoracic aorta and kidney endothelial and inducible NO synthases (eNOS and iNOS) were studied in 4 groups of 6 nephrectomized rats treated with either placebo, EPO, the calcium channel blocker felodipine, or EPO plus felodipine for 6 weeks. A group of sham-operated placebo-treated animals served as control. 1-3 Several factors have been implicated in the pathogenesis of EPO-induced hypertension. Chief among them is the resulting rise in hematocrit, which is thought to raise vascular resistance by increase in blood viscosity, loss of hypoxic vasodilation, and enhanced competition by hemoglobin for endothelium-derived nitric oxide (NO). [4][5][6][7] Other proposed mechanisms include volume expansion, increased endothelin production, 8 enhanced tissue renin-angiotensin activity, 9 and direct vasopressor action of EPO. 10In a series of recent studies, we demonstrated that EPOinduced hypertension is not due to the associated increase in hematocrit or erythrocyte mass.11 This was based on the observation that hypertension occurred in both iron-deficient and iron-sufficient uremic rats receiving long-term EPO therapy despite divergent hematocrits. Moreover, repeated red blood cell transfusions did not raise arterial blood pressure despite complete correction of anemia in the uremic animals.11 Accordingly, these experiments provided convincing evidence that EPO-induced hypertension is not related to the erythropoietic action of the hormone. We further found that long-term EPO administration leads to a significant rise in resting cytosolic [Ca 2ϩ ] i above the elevated values seen in untreated rats with chronic renal failure (CRF).11 Moreover, EPO therapy normalized the defective stimulated surge in [Ca 2ϩ ] i seen in the untreated CRF animals. The study further showed that long-term EPO administration resulted in a marked reduction in hypotensive response in vivo and vasorelaxation response in vitro to administration of the NO donor sodium nitroprusside. These observations pointed to NO resistance as a possible cause of EPO-induced hypertension. Since the vasodilatory action of NO is mediated by cGMP-induced fall in [Ca 2ϩ ] i , we hypothesized that the observed NO resistance may be due to the demonstrated rise in resting and/or stimulated [Ca 2ϩ ] i with EPO therapy. 11 The present study was designed to explore the effect of long-term EPO therapy with and without calcium channel blockade on NO production and NO synthase (NOS) expression. Methods Animal ModelsMale Sprague-Dawley rats (Harlan Sprague Dawley Inc) with an average we...

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Peripheral Hemodynamics, Blood Viscosity, and the Renin-Angiotensin System in Hemodialysis Patients under Therapy with Recombinant Human Erythropoietin

Cited by 41 publications

References 0 publications

Influence of the Renin-Angiotensin System Stimulation on Erythropoietin Production in Patients with Various Forms of Arterial Hypertension

Influence of the Renin-Angiotensin System Stimulation on Erythropoietin Production in Patients with Various Forms of Arterial Hypertension

Erythropoietin on a Tightrope: Balancing Neuronal and Vascular Protection between Intrinsic and Extrinsic Pathways

Nitric Oxide Metabolism in Erythropoietin-Induced Hypertension

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