Effect of angiotensin converting enzyme inhibitors on erythropoietin concentrations in healthy volunteers.

Pratt, M. C.; Lewis‐Barned, Nick; Walker, Robert; Bailey, Ross R.; Shand, Brett; Livesey, J. H.

doi:10.1111/j.1365-2125.1992.tb05644.x

Cited by 103 publications

(57 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In some patients, ACE inhibitors may cause a small decrease in serum EPO levels with a nonsignificant reduction in Hb (mean 0.27 g/dl) (28). ACE inhibitors were used in the majority of patients in both groups; however, it is unlikely that their use can therefore account for the anemia in the diabetic patients, and 4 of the 13 anemic DN patients were not using ACE inhibitors.…”

Section: Figure 1-relationship Between the Natural Logarithm Of Serummentioning

confidence: 99%

Anemia With Erythropoietin Deficiency Occurs Early in Diabetic Nephropathy

Bosman

Winkler²,

Marsden³

et al. 2001

Diabetes Care

280

192

View full text Add to dashboard Cite

OBJECTIVE -The normochromic normocytic anemia of erythropoietin (EPO) deficiency is recognized in advanced renal failure but not in early renal disease. The aim of this study was to determine whether anemia with EPO deficiency is found in type 1 diabetic patients with diabetic nephropathy in the absence of advanced renal failure and to compare them with patients with nondiabetic renal disease of similar severity. RESEARCH DESIGN AND METHODS-A total of 27 type 1 diabetic patients with diabetic nephropathy (DN), defined as having persistent proteinuria (mean 1,086 mg/day 190]), a serum creatinine Յ180 mol/l, and retinopathy, were compared with 26 nondiabetic patients with glomerulonephritis (GN) and persistent proteinuria (1,874 mg/day [349 -5,005]). The Hb concentration, red cell indexes, and serum EPO levels were measured, and other causes for the anemia were excluded. The EPO values were compared with a normal reference range obtained from nondiabetic patients with a microcytic anemia. The DN patients were tested for signs of diabetic peripheral and autonomic neuropathy.RESULTS -We found that 13 of the 27 DN patients were anemic (Hb 10.6 Ϯ 0.9 g/dl) in marked contrast to none of the GN patients (Hb 13.7 Ϯ 1.4 g/dl, P Ͻ 0.005). In the DN group, serum EPO concentrations failed to increase in response to anemia compared with the response seen in patients with microcytic anemia. Thus, the anemia of the DN group was associated with EPO deficiency. The anemic DN patients showed evidence of more severe proteinuria and diabetic neuropathy than the nonanemic DN patients.CONCLUSIONS -Anemia associated with EPO deficiency can occur early in DN before the onset of advanced renal failure, but does not normally occur in nondiabetic renal disease of similar severity. The pathogenesis requires elucidation. Diabetes Care 24:495-499, 2001

show abstract

Section: Figure 1-relationship Between the Natural Logarithm Of Serummentioning

confidence: 99%

Anemia With Erythropoietin Deficiency Occurs Early in Diabetic Nephropathy

Bosman

Winkler²,

Marsden³

et al. 2001

Diabetes Care

280

192

View full text Add to dashboard Cite

show abstract

“…Clinical studies of healthy human volunteers demonstrated that Ang II administration increased serum EPO concentration by ∼35% or higher via the activation of the angiotensin II type 1 receptor (AT 1 R) (Freudenthaler et al, 1999(Freudenthaler et al, , 2000Gossmann et al, 2001). Furthermore, the Ang II-converting enzyme inhibitors captopril and enalapril that block the maturation of Ang II from Ang I, significantly decreased plasma EPO levels, by as much as ∼20-30% in another study of healthy human volunteers (Pratt et al, 1992). These findings suggest that Ang II regulates EPO production in vivo via receptordependent signaling, but the mechanism of this regulation has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of Erythropoietin Regulation by Angiotensin II

et al. 2014

View full text Add to dashboard Cite

Erythropoietin (EPO) is the primary regulator of red blood cell development. Although hypoxic regulation of EPO has been extensively studied, the mechanism(s) for basal regulation of EPO are not well understood. In vivo studies in healthy human volunteers and animal models indicated that angiotensin II (Ang II) and angiotensin converting enzyme inhibitors regulated blood EPO levels. In the current study, we found that Ang II induced EPO expression in situ in murine kidney slices and in 786-O kidney cells in culture as determined by reverse transcription polymerase chain reaction. We further investigated the signaling mechanism of Ang II regulation of EPO in 786-O cells. Pharmacological inhibitors of Ang II type 1 receptor (AT 1 R) and extracellular signal-regulated kinase 1/2 (ERK1/2) suppressed Ang II transcriptional activation of EPO. Inhibitors of AT 2 R or Src homology 2 domain-containing tyrosine phosphatase had no effect. Coimmunoprecipiation experiments demonstrated that p21Ras was constitutively bound to the AT 1 R; this association was increased by Ang II but was reduced by the AT 1 R inhibitor telmisartan. Transmembrane domain (TM) 2 of AT 1 R is important for G protein-dependent ERK1/2 activation, and mutant D74E in TM2 blocked Ang II activation of ERK1/2. Ang II signaling induced the nuclear translocation of the Egr-1 transcription factor, and overexpression of dominant-negative Egr-1 blocked EPO promoter activation by Ang II. These data identify a novel pathway for basal regulation of EPO via AT 1 R-mediated Egr-1 activation by p21Ras-mitogen-activated protein kinase/ERK kinase-ERK1/2. Our current data suggest that Ang II, in addition to regulating blood volume and pressure, may be a master regulator of erythropoiesis.

show abstract

“…Administration of ANG II dose dependently increases Epo production (56, 57) and angiotensin-converting enzyme inhibitors (ACEi) decrease plasma Epo concentrations, likely by inhibiting ANG II formation (131). Several studies have suggested that the SNS can stimulate erythropoiesis, because reduced SNS activity is accompanied by anemia, which could be corrected by administration of Epo (18,135).…”

Section: Regulation Of Epo Productionmentioning

confidence: 99%

Erythropoietin and the cardiorenal syndrome: cellular mechanisms on the cardiorenal connectors

Jie

Verhaar²,

Cramer³

et al. 2006

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

We have recently proposed severe cardiorenal syndrome (SCRS), in which cardiac and renal failure mutually amplify progressive failure of both organs. This frequent pathophysiological condition has an extremely poor prognosis. Interactions between inflammation, the renin-angiotensin system, the balance between the nitric oxide and reactive oxygen species and the sympathetic nervous system form the cardiorenal connectors and are cornerstones in the pathophysiology of SCRS. An absolute deficit of erythropoietin (Epo) and decreased sensitivity to Epo in this syndrome both contribute to the development of anemia, which is more pronounced than renal anemia in the absence of heart failure. Besides expression on erythroid progenitor cells, Epo receptors are present in the heart, kidney, and vascular system, in which activation results in antiapoptosis, proliferation, and possibly antioxidation and anti-inflammation. Interestingly, Epo can improve cardiac and renal function. We have therefore reviewed the literature with respect to Epo and the cardiorenal connectors. Indeed, there are indications that Epo can diminish inflammation, reduce renin-angiotensin system activity, and shift the nitric oxide and reactive oxygen species balance toward nitric oxide. Information about Epo and the sympathetic nervous system is scarce. This analysis underscores the relevance of a further understanding of clinical and cellular mechanisms underlying protective effects of Epo, because this will support better treatment of SCRS. heart failure; renal failure; anemia; nitric oxide; reactive oxygen species COEXISTENCE OF RENAL AND cardiac disease is associated with high morbidity and mortality. This pathophysiological condition, in which combined cardiac and renal dysfunction amplifies a progression in the failure of the individual organ, has recently been denoted as severe cardiorenal syndrome (SCRS) (19,20).In patients with declined renal function measured by glomerular filtration rate (GFR), an independent increased risk for cardiovascular events has been found. The hazard ratio for cardiovascular events was 1.4 with a GFR Ͻ60 ml/min and increased with diminished renal function to 2.8 in patients with a GFR Ͻ30 ml/min (99). A 40% higher adjusted risk for adverse cardiovascular outcomes or death was observed in those with relatively minor degrees of renal dysfunction (120). The prevalence of chronic renal failure (CRF) is reportedly high in patients with congestive heart failure (CHF). Furthermore, the prevalence and severity of CRF correlate with the severity of CHF (44, 72). These data support that combined cardiac and renal failure is a profound problem, and a further understanding of the underlying pathophysiological and molecular mechanisms is needed to improve therapy.Our group proposed an interactive network of cardiorenal connectors, i.e., the renin-angiotensin system (RAS), nitric oxide and reactive oxygen species (NO-ROS) balance, the sympathetic nervous system (SNS), and inflammation, as the cornerstones of the pathophysiology o...

show abstract

Effect of angiotensin converting enzyme inhibitors on erythropoietin concentrations in healthy volunteers.

Cited by 103 publications

References 8 publications

Anemia With Erythropoietin Deficiency Occurs Early in Diabetic Nephropathy

Anemia With Erythropoietin Deficiency Occurs Early in Diabetic Nephropathy

Mechanism of Erythropoietin Regulation by Angiotensin II

Erythropoietin and the cardiorenal syndrome: cellular mechanisms on the cardiorenal connectors

Contact Info

Product

Resources

About