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Annuk, Margus
Publications (8 of 8) Show all publications
Annuk, M., Linde, T., Lind, L. & Fellström, B. (2006). Erythropoietin impairs endothelial vasodilatory function in patients with renal anemia and in healthy subjects. Nephron. Clinical practice, 102(1), c30-c34
Open this publication in new window or tab >>Erythropoietin impairs endothelial vasodilatory function in patients with renal anemia and in healthy subjects
2006 (English)In: Nephron. Clinical practice, ISSN 1660-8151, E-ISSN 2235-3186, Vol. 102, no 1, p. c30-c34Article in journal (Refereed) Published
Abstract [en]

Background/Aim: The mechanisms underlying the aggravation or development of hypertension frequently seen during treatment of renal anemia with epoetins are not fully elucidated. The aim of the present study was to investigate the effects of epoetin alfa on endothelial vasodilatory function in patients with renal anemia and in healthy subjects. Methods: Eighteen preuremic patients with anemia (GFR 23.4 ± 11 SD ml/min, Hb 101 ± 8 g/l) and 10 healthy subjects underwent evaluation of endothelium-dependent vasodilation (EDV) and endothelium-independent vasodilation (EIDV) by means of forearm blood flow (FBF) measurements with venous occlusion plethysmography during local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodium nitroprusside (SNP, evaluating EIDV). These investigations were performed before and 30 min after an intravenous injection of epoetin alfa (10,000 IU). Ten healthy subjects underwent the same procedure with the exception that saline were given instead of epoetin. The patients were treated with epoetin alfa subcutaneously for 12-19 weeks and revaluated when Hb exceeded 120 g/l. Results: EDV was attenuated after the epoetin injection in both renal patients and healthy subjects. This impairment persisted after anemia had been treated. EDIV and blood pressure remained constant. Saline had no effect on the variables measured. Conclusion: Our results indicate that epoetin alfa impairs endothelial function in renal patients and healthy subjects which may have an impact on vascular complications.

Keywords
Chronic renal failure, Endothelium, Epoetin alfa
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-79889 (URN)10.1159/000088308 (DOI)16166804 (PubMedID)
Available from: 2006-04-18 Created: 2006-04-18 Last updated: 2017-12-14Bibliographically approved
Annuk, M., Soveri, I., Zilmer, M., Lind, L., Hulthe, J. & Fellström, B. (2005). Endothelial function, CRP and oxidative stress in chronic kidney disease. JN. Journal of Nephrology (Milano. 1992), 18(6), 721-726
Open this publication in new window or tab >>Endothelial function, CRP and oxidative stress in chronic kidney disease
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2005 (English)In: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 18, no 6, p. 721-726Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Chronic kidney disease (CKD) is associated with increased morbidity and mortality in cardiovascular disease (CVD). Apart from traditional risk factors, chronic inflammation, oxidative stress, malnutrition and endothelial dysfunction are important in CVD development in renal patients. Our aim was to investigate the relationship between high sensitivity C-reactive protein (CRP), endothelium dependent vasodilation (EDV) and oxidative stress markers in patients with CKD K/DOQI stage 3-5.

METHODS: Measurements of CRP, conjugated dienes (CD), lipid hydroperoxide (LOOH), oxidized low density lipoprotein,glutathione and albumin were performed in 44 consecutive patients with CKD stage 3-5. EDV was measured by methacholine infusion in the brachial artery and venous occlusion plethysmography.

RESULTS: Patients with high CRP had significantly lower glomerular filtration rates and albumin, but increased LOOH and CD. In multiple regression analysis, only LOOH and CD remained significant. Patients with poor EDV had increased urea and lower glutathione (GSH). In multiple regression analysis, GSH and urea were independently related to EDV. No correlation was found between CRP and endothelial function.

CONCLUSION: CRP was related to lipid peroxidation, while endothelial function was related to intracellular oxidative stress in patients with CKD. CRP and EDV were unrelated to each other. Therefore, CRP and endothelial function could provide complementary prognostic information regarding future cardiovascular disorders in renal patients.

Keywords
Biological Markers/blood, Brachial Artery/physiopathology, C-Reactive Protein/*metabolism, Comparative Study, Disease Progression, Endothelium; Vascular/*physiopathology, Enzyme-Linked Immunosorbent Assay, Female, Glomerular Filtration Rate/physiology, Humans, Kidney Failure; Chronic/*blood/physiopathology, Lipid Peroxides/blood, Lipoproteins; LDL/blood, Male, Middle Aged, Oxidative Stress/*physiology, Plethysmography, Prognosis, Research Support; Non-U.S. Gov't, Vasodilation/*physiology
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-94636 (URN)16358230 (PubMedID)
Available from: 2006-06-01 Created: 2006-06-01 Last updated: 2017-12-14
Annuk, M., Zilmer, M. & Fellström, B. (2003). Endothelium-dependent vasodilation and oxidative stress in chronic renal failure: impact on cardiovascular disease. Kidney International, Supplement (84), S50-S53
Open this publication in new window or tab >>Endothelium-dependent vasodilation and oxidative stress in chronic renal failure: impact on cardiovascular disease
2003 (English)In: Kidney International, Supplement, ISSN 0098-6577, no 84, p. S50-S53Article in journal (Other academic) Published
Abstract [en]

Despite significant progress in renal replacement therapy, the mortality from cardiovascular disease (CVD) in patients with chronic renal failure (CRF) is many times higher than in the general population. The traditional risk factors are frequently present in CRF patients. However, based upon conventional risk factor analysis, these factors do not fully explain the extraordinary increase in morbidity and mortality in CVD among patients with CRF. Accumulating evidence suggests that CRF is associated with impaired endothelial cell function. In recent years, the role of endothelial dysfunction (ED) and excessive oxidative stress (OS) in the development of CVD has been highlighted. ED is an early feature of vascular disease in different diseases such diabetes, hypertension, hypercholesterolemia, and coronary heart disease. The precise mechanism which induces ED is not clear. Several factors however, including OS-related accumulation of uremic toxins, hypertension and shear stress, dyslipidemia with cytotoxic lipoprotein species such as small, dense low-density lipoprotein (LDL) particles, competitive inhibition of endothelial nitric oxide (NO) by increased production by asymmetrical dimethylarginine (ADMA) are pathogenic. In addition, it is known that excessive OS causes ED. An overproduction of reactive oxygen species (ROS) may injure the endothelial cell membrane, inactivate NO, and cause oxidation of an essential cofactor of nitric oxide synthase (NOS). Recent studies have demonstrated that an impaired endothelium-dependent vasodilation and OS are closely related to each other in patients with CRF.

Keywords
Cardiovascular Diseases/metabolism/*physiopathology, Endothelium; Vascular/*metabolism, Humans, Kidney Failure; Chronic/metabolism/*physiopathology, Oxidative Stress/physiology, Vasodilation/*physiology
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-74287 (URN)12694308 (PubMedID)
Available from: 2005-09-20 Created: 2005-09-20 Last updated: 2017-12-14Bibliographically approved
Annuk, M., Fellström, B. & Lind, L. (2002). Cyclooxygenase inhibition improves endothelium-dependent vasodilatation in patients with chronic renal failure. Nephrology, Dialysis and Transplantation, 17(12), 2159-2163
Open this publication in new window or tab >>Cyclooxygenase inhibition improves endothelium-dependent vasodilatation in patients with chronic renal failure
2002 (English)In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 17, no 12, p. 2159-2163Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Some studies have demonstrated beneficial effects of L-arginine as a substrate for nitric oxide synthesis, and diclofenac as an inhibitor of cyclooxygenase (COX)-derived vasoconstrictive agents on vascular responses in humans during several pathological conditions. The aim of the present study was to investigate the acute effects of L-arginine and diclofenac on endothelium-dependent vasodilatation (EDV) and endothelium-independent vasodilatation (EIDV) in patients with chronic renal failure (CRF).

METHODS: Effects of L-arginine and diclofenac on EDV and EIDV were measured in 15 patients with CRF and in 15 healthy controls by means of forearm blood flow measurements with venous occlusion plethysmography during local intra-arterial infusions of methacholine (2 and 4 micro g/min evaluating EDV) and sodium nitroprusside (5 and 10 micro g/min evaluating EIDV).

RESULTS: L-Arginine infusion increased methacholine-induced vasodilatation both in patients with CRF and healthy controls. Diclofenac infusion increased methacholine-induced vasodilatation only in patients with CRF. There was no significant change in nitroprusside-induced vasodilatation after L-arginine and diclofenac infusions both in patients with CRF and healthy controls.

CONCLUSIONS: These results suggest that COX inhibition reduces the levels of a prostanoid-derived vasoconstrictive agent contributing to the impaired EDV in patients with CRF, while in this age group L-arginine improves EDV regardless of renal function.

Keywords
Aged, Arginine/therapeutic use, Cyclooxygenase Inhibitors/*therapeutic use, Diclofenac/*therapeutic use, Endothelium; Vascular/*physiopathology, Female, Forearm/blood supply, Humans, Kidney Failure; Chronic/*drug therapy/*physiopathology, Male, Methacholine Chloride/diagnostic use, Middle Aged, Nitroprusside/diagnostic use, Regional Blood Flow/drug effects, Research Support; Non-U.S. Gov't, Vasodilation/*drug effects, Vasodilator Agents/diagnostic use
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-73223 (URN)10.1093/ndt/17.12.2159 (DOI)12454227 (PubMedID)
Available from: 2005-06-01 Created: 2005-06-01 Last updated: 2017-12-14Bibliographically approved
Annuk, M., Lind, L., Linde, T. & Fellström, B. (2001). Impaired endothelium-dependent vasodilatation in renal failure in humans. Nephrology, Dialysis and Transplantation, 16(2), 302-306
Open this publication in new window or tab >>Impaired endothelium-dependent vasodilatation in renal failure in humans
2001 (English)In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 16, no 2, p. 302-306Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The main causes of death in patients with chronic renal failure (CRF) are cardiovascular complications. The aim of the present study was to compare endothelium-dependent vasodilatation (EDV) in patients with chronic renal failure with a control population controlling for hypertension, diabetes mellitus and hypercholesterolaemia.

METHODS: Fifty-six patients with moderate CRF (mean creatinine clearance 29.4 ml/min/1.73 m(2)) underwent evaluation of EDV and endothelium-independent vasodilatation (EIDV) by means of forearm blood flow (FBF) measurements with venous occlusion plethysmography during local intra-arterial infusions of methacholine (Mch, 2 and 4 microg/min evaluating EDV) and sodium nitroprusside (SNP, 5 and 10 microg/min evaluating EIDV). Fifty-six control subjects without renal impairment underwent the same investigation.

RESULTS: Infusion of Mch increased FBF significantly less in patients with renal failure than in controls (198 vs 374%, P<0.001), whereas no significant difference was seen regarding the vasodilatation induced by SNP (278 vs 269%). The differences in EDV between the groups were still significant after controlling for hypertension, blood glucose, and serum cholesterol in multiple regression analysis (P<0.001). EDV was related to serum creatinine (r=-0.37, P<0.01), creatinine clearance (r=0.45, P<0.005) and to serum triglyceride levels (r=-0.29, P<0.005) in the CRF group.

CONCLUSIONS: Patients with moderate CRF have an impaired EDV even after correction for traditional cardiovascular risk factors and this impairment is related to the degree of renal failure.

Keywords
Aged, Creatinine/blood, Endothelium; Vascular/*physiopathology, Female, Forearm/blood supply, Humans, Injections; Intra-Arterial, Kidney Failure; Chronic/*physiopathology, Male, Methacholine Chloride/pharmacology, Middle Aged, Nitroprusside/pharmacology, Plethysmography, Reference Values, Regional Blood Flow/drug effects, Research Support; Non-U.S. Gov't, Vasodilation, Veins
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-73061 (URN)10.1093/ndt/16.2.302 (DOI)11158404 (PubMedID)
Available from: 2008-06-11 Created: 2008-06-11 Last updated: 2017-12-14Bibliographically approved
Annuk, M., Zilmer, M., Lind, L., Linde, T. & Fellström, B. (2001). Oxidative stress and endothelial function in chronic renal failure. Journal of the American Society of Nephrology, 12(12), 2747-2752
Open this publication in new window or tab >>Oxidative stress and endothelial function in chronic renal failure
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2001 (English)In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 12, no 12, p. 2747-2752Article in journal (Other academic) Published
Abstract [en]

This study aimed to investigate the relationship between oxidative stress and endothelium-dependent vasodilation in patients with chronic renal failure (CRF). Thirty-seven patients with CRF underwent evaluation of endothelium-dependent vasodilation and endothelium-independent vasodilation by means of forearm blood flow measurements with venous occlusion plethysmography during local intra-arterial infusions of methacholine (evaluating endothelium-dependent vasodilation) and sodium nitroprusside (evaluating endothelium-independent vasodilation). Lag phase of lipoprotein fraction to oxidation, total antioxidative activity, diene conjugates, thiobarbituric acid reactive substances, lipid hydroperoxide, reduced glutathione (GSH), oxidized GSH (GSSG), and the GSH redox ratio (GSSG/GSH) were all measured as markers of oxidative stress. Two groups of healthy subjects (61 and 37 subjects, respectively) were used as controls. In one group, oxidative stress markers were measured, whereas endothelium-dependent vasodilation and endothelium-independent vasodilation were assessed in the other group. Compared with controls, the patients with renal insufficiency had an impaired endothelium-dependent vasodilation, a shorter lag phase of lipoprotein fraction, and higher levels of diene conjugates, lipid hydroperoxide, and GSSG levels. The GSSG/GSH ratio was lower in patients with CRF. Endothelium-dependent vasodilation was positively correlated with total antioxidative activity (r = 0.41, P = 0.016), GSH (r = 0.44, P < 0.0098), and lag phase of LDL (r = 0.35, P = 0.036) and negatively correlated with GSSG (r = -0.40, P < 0.018), GSSG/GSH (r = -0.47, P = 0.0057), and diene conjugates (r = -0.53 P < 0.0015) in patients with CRF. These results show that an impaired endothelium vasodilation function and oxidative stress are related to each other in patients with CRF.

Keywords
Aged, Endothelium; Vascular/*physiopathology, Female, Glutathione/metabolism, Glutathione Disulfide/metabolism, Humans, Kidney Failure; Chronic/*physiopathology, Male, Middle Aged, Oxidative Stress, Reference Values, Research Support; Non-U.S. Gov't, Vasodilation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-73139 (URN)11729244 (PubMedID)
Available from: 2005-06-01 Created: 2005-06-01 Last updated: 2017-12-14Bibliographically approved
Annuk, M., Fellström, B., Åkerblom, O., Zilmer, K., Vihalemm, T. & Zilmer, M. (2001). Oxidative stress markers in pre-uremic patients. Clinical Nephrology, 56(4), 308-314
Open this publication in new window or tab >>Oxidative stress markers in pre-uremic patients
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2001 (English)In: Clinical Nephrology, ISSN 0301-0430, Vol. 56, no 4, p. 308-314Article in journal (Other (popular science, discussion, etc.)) Published
Abstract [en]

AIM: The present study was designed to investigate a complex of oxidative stress (OS) markers in patients with chronic renal failure (CRF) and to study the relationship between different OS markers and degree of renal failure. The following indices of OS were measured in plasma: oxidized glutathione (GSSG), reduced glutathione (GSH), total glutathione (TGSH), glutathione redox ratio (GSSG/GSH) and resistance of lipoprotein fraction to oxidation (lag phase of LPF). Baseline diene conjugation level of lipoprotein fraction (BDC-LPF), total antioxidative activity (TAA), diene conjugates (DC), lipid hydroperoxides (LOOH) and thiobarbituric acid-reactive substances (TBARS) were measured in serum. All markers in plasma and serum were measured both in patients with CRF and in healthy controls.

SUBJECTS AND METHODS: Blood samples were obtained from 38 patients with CRF and from 61 healthy controls. Routine biochemical analyses were performed by using commercially available kits.

RESULTS: Levels of DC, BDC-LPF, LOOH, GSSG and GSSG/GSH ratio were significantly increased and lag phase of LPF was significantly shortened in patients with CRF compared with healthy controls. Serum creatinine and urea levels correlated significantly with GSSG level and GSSG/GSH in patients with CRF. A significant inverse correlation was found between glutathione redox ratio and lag phase of LPF and between GSSG level and BDC-LPF.

CONCLUSIONS: The findings suggest that renal patients are in a state of oxidative stress compared with healthy controls. The most informative indices to evaluate the degree of OS in CRF were: GSSG level, GSSG/GSH status, lag phase of LPF and BDC-LPF.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-72212 (URN)11680661 (PubMedID)
Available from: 2005-09-18 Created: 2005-09-18 Last updated: 2017-12-14Bibliographically approved
Lind, L., Hall, J., Larsson, A., Annuk, M., Fellström, B. & Lithell, H. (2000). Evaluation of endothelium-dependent vasodilation in the human peripheral circulation. Clinical Physiology, 20(6), 440-448
Open this publication in new window or tab >>Evaluation of endothelium-dependent vasodilation in the human peripheral circulation
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2000 (English)In: Clinical Physiology, ISSN 0144-5979, E-ISSN 1365-2281, Vol. 20, no 6, p. 440-448Article in journal (Refereed) Published
Abstract [en]

Flow-mediated vasodilation (FMD) in the brachial artery measured by ultrasound, and the increase in forearm blood flow (FBF) induced by local infusion of a muscarinic-receptor agonist have both frequently been used to evaluate endothelium-dependent vasodilation (EDV) in the human forearm. The present study intended to evaluate the relationship between these techniques and to investigate if vasodilation induced by the muscarinic receptor-agonist methacholine (MCh) was owing to production of nitric oxide (NO). FMD during hyperaemia was assessed by ultrasound and FBF was measured by venous occlusion plethysmography during local infusion of MCh or L-arginine in the human forearm. Both these methods were applied in 26 individuals. In another 12 individuals forearm arterial and venous plasma concentrations of nitrate/nitrite (NOx) were measured together with FBF before and during local MCh infusion. While the change in brachial artery diameter induced by sublingually given nitroglycerine and the vasodilatory response to sodium nitroprusside (SNP) given locally in the forearm were significantly correlated (r = 0.70, P < 0.01), FMD showed no relationship with the vasodilation evoked by MCh (r = -0.03) or L-arginine (r = 0.04). The five-fold increase in FBF during MCh infusion was associated with a significant increase in venous plasma NOx concentrations (P < 0.05) and a more than 11-fold increase in forearm NOx-release (P < 0.01). Thus, a significant relationship between the two methods regarding the evaluation of endothelium-independent vasodilation evoked by NO-donors was found, but no relationship was found between the two methods regarding the evaluation of endothelium-dependent vasodilation. Furthermore, vasodilation induced by MCh in the forearm seems to be induced by NO-release.

Keywords
artery, blood flow, Endothelium, methods, nitric oxide, ultrasound, vasodilation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-53560 (URN)10.1046/j.1365-2281.2000.00281.x (DOI)11100391 (PubMedID)
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2017-12-04Bibliographically approved
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