20 results on '"Sedeek M"'
Search Results
2. Critical role of Nox4-based NADPH oxidase in glucose-induced oxidative stress in the kidney: implications in type 2 diabetic nephropathy
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Sedeek, M., Cailera, G., Montezano, A., Gutsol, A., Heitz, F., Szyndralewiez, C., Page, P., Kennedy, C.R.J., Burns, K.D., Touyz, R.M., and Hebert, R.L.
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Oxidases -- Physiological aspects ,Oxidases -- Research ,Diabetic nephropathies -- Risk factors ,Diabetic nephropathies -- Genetic aspects ,Diabetic nephropathies -- Care and treatment ,Diabetic nephropathies -- Research ,NADP (Coenzyme) -- Physiological aspects ,NADP (Coenzyme) -- Research ,Transforming growth factors -- Physiological aspects ,Transforming growth factors -- Genetic aspects ,Transforming growth factors -- Research ,Biological sciences - Abstract
Molecular mechanisms underlying renal complications of diabetes remain unclear. We tested whether renal NADPH oxidase (Nox) 4 contributes to increased reactive oxygen species (ROS) generation and hyperactivation of redox-sensitive signaling pathways in diabetic nephropathy. Diabetic mice (db/db) (20 wk) and cultured mouse proximal tubule (MPT) cells exposed to high glucose (25 retool/l, D-glucose) were studied. Expression (gene and protein) of Nox4, [p22.sup.phox], and [p47.sup.phox], but not Noxl or Nox2, was increased in kidney cortex, but not medulla, from db/db vs. control mice (db/m) (P < 0.05). ROS generation, p38 mitogen-activated protein (MAP) kinase phosphorylation, and content of fibronectin and transforming growth factor (TGF)-[beta]1/2 were increased in db/db vs. db/m (P < 0.01). High glucose increased expression of Nox4, but not other Noxes vs. normal glucose (P < 0.05). This was associated with increased NADPH oxidase activation and enhanced ROS production. Nox4 downregulation by small-interfering RNA and inhibition of Nox4 activity by GK-136901 (Noxl/4 inhibitor) attenuated D-glucose-induced NADPH oxidase-derived ROS generation. High D-glucose, but not L-glucose, stimulated phosphorylation of p38MAP kinase and increased expression of TGF-[beta]1/2 and fibronectin, effects that were inhibited by SB-203580 (p38MAP kinase inhibitor). GK-136901 inhibited D-glucose-induced actions. Our data indicate that, in diabetic conditions: 1) renal Nox4 is upregulated in a cortex-specific manner, 2) MPT cells possess functionally active Nox4-based NADPH, 3) Nox4 is a major source of renal ROS, and 4) activation of profibrotic processes is mediated via Nox4-sensitive, p38MAP kinase-dependent pathways. These findings implicate Nox4-based NADPH oxidase in molecular mechanisms underlying fibrosis in type 2 diabetic nephropathy. superoxide; hydrogen peroxide; hyperglycemia; nicotinamide adenine dinucleotide phosphate reduced form oxidase; diabetes doi: 10.1152/ajprenal.00028.2010
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- 2010
3. Plasma orexin-A levels in postmenopausal women: possible interaction with estrogen and correlation with cardiovascular risk status
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El-Sedeek, M ShEA, Korish, A A, and Deef, M M
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- 2010
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4. Coracoid Impingement
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Sedeek M. Mosaid and Charlie Talbot
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- 2017
5. Role of Reactive Oxygen Species in Hypertension Produced by Reduced Uterine Perfusion in Pregnant Rats
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Sedeek, M., primary, Gilbert, J. S., additional, LaMarca, B. B., additional, Sholook, M., additional, Chandler, D. L., additional, Wang, Y., additional, and Granger, J. P., additional
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- 2008
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6. Systemic hemodynamic and regional blood flow changes in response to chronic reductions in uterine perfusion pressure in pregnant rats
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Sholook, M. M., primary, Gilbert, J. S., additional, Sedeek, M. H., additional, Huang, M., additional, Hester, R. L., additional, and Granger, J. P., additional
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- 2007
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7. Increased oxidative stress in a rat model of preeclampsia
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SEDEEK, M, primary
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- 2004
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8. Molecular mechanisms of hypertension: role of Nox family NADPH oxidases.
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Sedeek M, Hebert R, Kennedy CR, Burns KD, and Touyz RM
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- 2009
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9. Effect of angiotensin II synthesis blockade on the hypertensive response to chronic reductions in uterine perfusion pressure in pregnant rats.
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Alexander, B T, Cockrell, K, Cline, F D, Llinas, M T, Sedeek, M, and Granger, J P
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- 2001
10. Synovial Chondromatosis of the Ankle Joint: Clinical, Radiological, and Intraoperative Findings
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Sedeek Mohamed Sedeek, Q. Choudry, and S. Garg
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Orthopedic surgery ,RD701-811 - Abstract
Synovial chondromatosis, also termed synovial osteochondromatosis, is a rare benign disorder characterized by the presence of cartilaginous nodules in the synovium of the joints, tendon sheaths, and bursae. It most commonly involves large joints, such as the knee, hip, and shoulder, but its presence in smaller joints has also been reported. Nevertheless, ankle involvement is unusual. The diagnosis is commonly made following a thorough history, clinical, physical, and radiographic examination. We report a case of a young patient with primary synovial chondromatosis of the ankle joint and present the clinical, radiographic, and intraoperative findings.
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- 2015
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11. Intraosseous Ganglion of the Distal Tibia: Clinical, Radiological, and Operative Management
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Sedeek Mohamed Sedeek, Q. Choudry, and S. Garg
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Orthopedic surgery ,RD701-811 - Abstract
Intraosseous ganglia are benign cystic lesions located in the subchondral bone. Intraosseous ganglion cysts of the ankle are relatively uncommon. We present a case of recurrent intraosseous ganglion in the ankle of a 41-year-old female who had recurrence after initial surgery. She was treated effectively by curettage and autogenous cancellous bone grafting. At the final follow-up, satisfactory results were obtained with no recurrence or complications.
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- 2015
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12. Pathophysiology of hypertension in response to placental ischemia during pregnancy: a central role for endothelin?
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LaMarca BD, Alexander BT, Gilbert JS, Ryan MJ, Sedeek M, Murphy SR, and Granger JP
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Background: Preeclampsia is new-onset hypertension with proteinuria during pregnancy. The initiating event in preeclampsia has been postulated to involve reduced placental perfusion, which leads to widespread dysfunction of the maternal vascular endothelium.Objective: The main objective of this brief review was to highlight some of the recent advances in our understanding of the mechanisms whereby the endothelin (ET) system, via ET type A (ETA) receptor activation, modulates blood pressure in preeclamptic women and in animal models of pregnancy-related hypertension.Methods: This review focused on the role of ET and tumor necrosis factor-alpha (TNF-alpha) in preeclampsia, with emphasis on the pathophysiology of hypertension in response to placental ischemia in animal models of pregnancy. Relevant published data were identified by searching PubMed and supplemented with contributions from our laboratory.Results: Studies in preeclamptic women indicate that their hypertension is associated with increases in ET synthesis. Recent studies in pregnant rats indicate that the ET system is activated in response to reductions in uterine perfusion pressure and to chronic elevations in serum TNF-alpha concentrations. In these 2 animal models, the findings also suggest that ET A receptor activation may play a role in mediating hypertension.Conclusions: Although recent studies in animal models implicate an important role for the ET system in preeclampsia, the usefulness of selective ET A receptor antagonists for the treatment of hypertension in women with preeclampsia remains unclear. This important question will not be answered until well-controlled clinical studies using specific ET A receptor antagonists are conducted for women with preeclampsia. [ABSTRACT FROM AUTHOR]
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- 2008
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13. NADPH oxidases, reactive oxygen species, and the kidney: friend and foe.
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Sedeek M, Nasrallah R, Touyz RM, and Hébert RL
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- Animals, Humans, Kidney metabolism, Kidney pathology, Kidney Diseases enzymology, Kidney Diseases metabolism, Kidney Diseases pathology, Kidney enzymology, NADPH Oxidases metabolism, Reactive Oxygen Species metabolism
- Abstract
Reactive oxygen species (ROS) play an important role in normal cellular physiology. They regulate different biologic processes such as cell defense, hormone synthesis and signaling, activation of G protein-coupled receptors, and ion channels and kinases/phosphatases. ROS are also important regulators of transcription factors and gene expression. On the other hand, in pathologic conditions, a surplus of ROS in tissue results in oxidative stress with various injurious consequences such as inflammation and fibrosis. NADPH oxidases are one of the many sources of ROS in biologic systems, and there are seven isoforms (Nox1-5, Duox1, Duox2). Nox4 is the predominant form in the kidney, although Nox2 is also expressed. Nox4 has been implicated in the basal production of ROS in the kidney and in pathologic conditions such as diabetic nephropathy and CKD; upregulation of Nox4 may be important in renal oxidative stress and kidney injury. Although there is growing evidence indicating the involvement of NADPH oxidase in renal pathology, there is a paucity of information on the role of NADPH oxidase in the regulation of normal renal function. Here we provide an update on the role of NADPH oxidases and ROS in renal physiology and pathology.
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- 2013
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14. Renoprotective effects of a novel Nox1/4 inhibitor in a mouse model of Type 2 diabetes.
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Sedeek M, Gutsol A, Montezano AC, Burger D, Nguyen Dinh Cat A, Kennedy CR, Burns KD, Cooper ME, Jandeleit-Dahm K, Page P, Szyndralewiez C, Heitz F, Hebert RL, and Touyz RM
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- Albuminuria prevention & control, Albuminuria urine, Animals, Blood Glucose analysis, Blood Pressure drug effects, Blotting, Western, Body Weight drug effects, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 urine, Diabetic Nephropathies etiology, Diabetic Nephropathies physiopathology, Disease Models, Animal, Gene Expression Regulation, Enzymologic drug effects, Kidney drug effects, Kidney metabolism, Kidney pathology, Male, Mice, Mice, Inbred C57BL, Mitogen-Activated Protein Kinases metabolism, NADH, NADPH Oxidoreductases antagonists & inhibitors, NADH, NADPH Oxidoreductases genetics, NADH, NADPH Oxidoreductases metabolism, NADPH Oxidase 1, NADPH Oxidase 4, NADPH Oxidases genetics, NADPH Oxidases metabolism, Reverse Transcriptase Polymerase Chain Reaction, Superoxide Dismutase genetics, Superoxide Dismutase metabolism, Superoxide Dismutase-1, Thiobarbituric Acid Reactive Substances analysis, Transforming Growth Factor beta metabolism, Vascular Cell Adhesion Molecule-1 metabolism, Diabetes Mellitus, Type 2 complications, Diabetic Nephropathies prevention & control, NADPH Oxidases antagonists & inhibitors, Pyrazoles pharmacology, Pyridones pharmacology
- Abstract
Nox (NADPH oxidase)-derived ROS (reactive oxygen species) have been implicated in the development of diabetic nephropathy. Of the Nox isoforms in the kidney, Nox4 is important because of its renal abundance. In the present study, we tested the hypothesis that GKT136901, a Nox1/4 inhibitor, prevents the development of nephropathy in db/db (diabetic) mice. Six groups of male mice (8-week-old) were studied: (i) untreated control db/m, (ii) low-dose GKT136901-treated db/m (30 mg/kg of body weight per day), (iii) high-dose GKT136901-treated db/m (90 mg/kg of body weight per day), (iv) untreated db/db; (v) low dose GKT136901-treated db/db; and (vi) high-dose GKT136901-treated db/db. GKT136901, in chow, was administered for 16 weeks. db/db mice developed diabetes and nephropathy as evidenced by hyperglycaemia, albuminuria and renal injury (mesangial expansion, tubular dystrophy and glomerulosclerosis). GKT136901 treatment had no effect on plasma glucose or BP (blood pressure) in any of the groups. Plasma and urine TBARSs (thiobarbituric acid-reacting substances) levels, markers of systemic and renal oxidative stress, respectively, were increased in diabetic mice. Renal mRNA expression of Nox4, but not of Nox2, increased, Nox1 was barely detectable in db/db. Expression of the antioxidant enzyme SOD-1 (superoxide dismutase 1) decreased in db/db mice. Renal content of fibronectin, pro-collagen, TGFβ (transforming growth factor β) and VCAM-1 (vascular cell adhesion molecule 1) and phosphorylation of ERK1/2 (extracellular-signal-regulated kinase 1/2) were augmented in db/db kidneys, with no change in p38 MAPK (mitogen-activated protein kinase) and JNK (c-Jun N-terminal kinase). Treatment reduced albuminuria, TBARS and renal ERK1/2 phosphorylation and preserved renal structure in diabetic mice. Our findings suggest a renoprotective effect of the Nox1/4 inhibitor, possibly through reduced oxidative damage and decreased ERK1/2 activation. These phenomena occur independently of improved glucose control, suggesting GKT136901-sensitive targets are involved in complications of diabetes rather than in the disease process.
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- 2013
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15. Oxidative stress, Nox isoforms and complications of diabetes--potential targets for novel therapies.
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Sedeek M, Montezano AC, Hebert RL, Gray SP, Di Marco E, Jha JC, Cooper ME, Jandeleit-Dahm K, Schiffrin EL, Wilkinson-Berka JL, and Touyz RM
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- Animals, Antioxidants therapeutic use, Cardiovascular Diseases drug therapy, Diabetes Complications drug therapy, Diabetic Angiopathies drug therapy, Enzyme Inhibitors therapeutic use, Humans, Isoenzymes, Cardiovascular Diseases enzymology, Diabetes Complications enzymology, Diabetic Angiopathies enzymology, NADPH Oxidases metabolism, Oxidative Stress drug effects, Reactive Oxygen Species metabolism
- Abstract
Most diabetes-related complications and causes of death arise from cardiovascular disease and end-stage renal disease. Amongst the major complications of diabetes mellitus are retinopathy, neuropathy, nephropathy and accelerated atherosclerosis. Increased bioavailability of reactive oxygen species (ROS) (termed oxidative stress), derived in large part from the NADPH oxidase (Nox) family of free radical producing enzymes, has been demonstrated in experimental and clinical diabetes and has been implicated in the cardiovascular and renal complications of diabetes. The present review focuses on the role of Noxs and oxidative stress in some major complications of diabetes, including nephropathy, retinopathy and atherosclerosis. We also discuss Nox isoforms as potential targets for therapy.
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- 2012
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16. NOX isoforms and reactive oxygen species in vascular health.
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Touyz RM, Briones AM, Sedeek M, Burger D, and Montezano AC
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- Animals, Blood Vessels enzymology, Humans, Isoenzymes metabolism, Blood Vessels metabolism, Health, NADPH Oxidases metabolism, Reactive Oxygen Species metabolism
- Abstract
Reactive oxygen species (ROS) are important mediators of cell growth, adhesion, differentiation, migration, senescence, and apoptosis. ROS play an important physiological role in regulating vascular tone and can also contribute to pathological mechanisms related to endothelial dysfunction, vascular reactivity, arterial remodeling, and vascular inflammation. The major source of ROS generated in the cardiovascular system is the NADPH oxidase (NOX) family of enzymes, of which seven members have been characterized. Although each NOX family member is typified by six transmembrane domains along with a cytoplasmic domain that binds NADPH and FAD, each isoform is distinguished by the specific catalytic subunit, interacting proteins, and subcellular localization. We review the current understanding of NOX signaling and regulatory mechanisms related to vascular health and disease.
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- 2011
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17. Plasma orexin-A levels in postmenopausal women: possible interaction with estrogen and correlation with cardiovascular risk status.
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El-Sedeek MSh, Korish AA, and Deef MM
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- Adult, Blood Glucose metabolism, Blood Pressure physiology, Body Mass Index, Cardiovascular Diseases physiopathology, Case-Control Studies, Cholesterol metabolism, Female, Humans, Middle Aged, Orexins, Risk Assessment, Risk Factors, Triglycerides metabolism, Cardiovascular Diseases etiology, Estrogens metabolism, Estrogens physiology, Intracellular Signaling Peptides and Proteins metabolism, Neuropeptides metabolism, Postmenopause blood
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Objective: To assess plasma orexin-A levels in a group of postmenopausal women not receiving estrogen-replacement therapy (ERT), and to compare the values with a group on ERT and a group of reproductive-age women, and to correlate the findings with some cardiovascular risk factors., Design: Observational cohort study., Setting: Alexandria University Hospital., Population: Ninety women, in three groups: a control group of 30 healthy, reproductive-age women, 30 healthy postmenopausal women not receiving ERT, and 30 healthy postmenopausal women on ERT for 6 months., Methods: Quantitative clinical assessment as well as laboratory investigations., Main Outcome Measures: Orexin-A levels, serum estradiol, cholesterol, triglycerides, and fasting glucose are the main laboratory outcome measures, whereas blood pressure and weight are the main clinical outcome measures., Results: Postmenopausal women not receiving ERT had the highest levels of plasma orexin A (705.61 +/- 165.62 microg/dl). Postmenopausal women on ERT had orexin-A levels that were comparable with the control group (233.90 +/- 54.26 versus 243.81 +/- 68.88 microg/dl). Plasma orexin-A levels were directly correlated with blood glucose lipid profile, arterial blood pressure, and body mass index., Conclusions: Higher orexin-A levels are associated with hypoestrogenism, and are partially reversed by ERT. A possible inhibitory effect of estrogen on orexin might partially account for its cardioprotective effect.
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- 2010
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18. Pathophysiology of hypertension during preeclampsia: linking placental ischemia with endothelial dysfunction.
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Gilbert JS, Ryan MJ, LaMarca BB, Sedeek M, Murphy SR, and Granger JP
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- Adult, Animals, Endothelium, Vascular physiology, Female, Hormones physiology, Humans, Hypertension etiology, Ischemia physiopathology, Oxidative Stress physiology, Pregnancy, Regional Blood Flow physiology, Uterus blood supply, Hypertension physiopathology, Pre-Eclampsia physiopathology
- Abstract
Studies over the last decade have provided exciting new insights into potential mechanisms underlying the pathogenesis of preeclampsia. The initiating event in preeclampsia is generally regarded to be placental ischemia/hypoxia, which in turn results in the elaboration of a variety of factors from the placenta that generates profound effects on the cardiovascular system. This host of molecules includes factors such as soluble fms-like tyrosine kinase-1, the angiotensin II type 1 receptor autoantibody, and cytokines such as tumor necrosis factor-alpha, which generate widespread dysfunction of the maternal vascular endothelium. This dysfunction manifests as enhanced formation of factors such as endothelin, reactive oxygen species, and augmented vascular sensitivity to angiotensin II. Alternatively, the preeclampsia syndrome may also be evidenced as decreased formation of vasodilators such as nitric oxide and prostacyclin. Taken together, these alterations cause hypertension by impairing renal pressure natriuresis and increasing total peripheral resistance. Moreover, the quantitative importance of the various endothelial and humoral factors that mediate vasoconstriction and elevation of arterial pressure during preeclampsia remains to be elucidated. Thus identifying the connection between placental ischemia/hypoxia and maternal cardiovascular abnormalities in hopes of revealing potential therapeutic regimens remains an important area of investigation and will be the focus of this review.
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- 2008
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19. Systemic hemodynamic and regional blood flow changes in response to chronic reductions in uterine perfusion pressure in pregnant rats.
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Sholook MM, Gilbert JS, Sedeek MH, Huang M, Hester RL, and Granger JP
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- Animals, Aorta, Abdominal surgery, Arteries surgery, Disease Models, Animal, Female, Gestational Age, Ligation, Microspheres, Pregnancy, Radioisotopes administration & dosage, Rats, Rats, Sprague-Dawley, Regional Blood Flow, Scandium administration & dosage, Blood Pressure, Cardiac Output, Placenta blood supply, Pre-Eclampsia physiopathology, Uterus blood supply, Vascular Resistance
- Abstract
Preeclampsia (PE) is associated with increased total peripheral resistance (TPR), reduced cardiac output (CO), and diminished uterine and placental blood flow. We have developed an animal model that employs chronic reductions in uterine perfusion pressure (RUPP) in pregnant rats to generate a "preeclamptic-like" state during late gestation that is characterized by hypertension, proteinuria, and endothelial dysfunction. Although this animal model has many characteristics of human PE, the systemic hemodynamic and regional changes in blood flow that occur in response to chronic RUPP remains unknown. Therefore, we hypothesized that RUPP would decrease uteroplacental blood flow and CO, and increase TPR. Mean arterial pressure (MAP), CO, cardiac index (CI), TPR, and regional blood flow to various tissues were measured using radiolabeled microspheres in the following two groups of conscious rats: normal pregnant rats (NP; n = 8) and RUPP rats (n = 8). MAP was increased (132 +/- 4 vs. 99 +/- 3 mmHg) in the RUPP rats compared with the NP dams. The hypertension in RUPP rats was associated with increased TPR (2.15 +/- 0.02 vs. 0.98 +/- 0.08 mmHg x ml(-1) x min(-1)) and decreased CI (246 +/- 20 vs. 348 +/- 19 ml x min(-1) x kg(-1), P < 0.002) when contrasted with NP dams. Furthermore, uterine (0.16 +/- 0.03 vs. 0.38 +/- 0.09 ml x min(-1) x g tissue(-1)) and placental blood flow (0.30 +/- 0.08 vs. 0.70 +/- 0.10 ml x min(-1) x g tissue(-1)) were decreased in RUPP compared with the NP dams. These data demonstrate that the RUPP model of pregnancy-induced hypertension has systemic hemodynamic and regional blood flow alterations that are strikingly similar to those observed in women with PE.
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- 2007
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20. Reduced uterine perfusion pressure (RUPP) model for studying cardiovascular-renal dysfunction in response to placental ischemia.
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Granger JP, LaMarca BB, Cockrell K, Sedeek M, Balzi C, Chandler D, and Bennett W
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- Animals, Constriction, Female, Hypertension physiopathology, Ischemia physiopathology, Placenta blood supply, Pregnancy, Rats, Uterus blood supply, Disease Models, Animal, Pre-Eclampsia physiopathology, Rats, Sprague-Dawley physiology
- Abstract
Despite being one of the leading causes of maternal death and a major contributor of maternal and perinatal morbidity, the mechanisms responsible for the pathogenesis of preeclampsia are unknown. The initiating event in preeclampsia has been postulated to be reduced uteroplacental perfusion. Placental ischemia/hypoxia is thought to lead to widespread activation/dysfunction of the maternal vascular endothelium, vasoconstriction and hypertension. Experimental induction of chronic uteroplacental ischemia appears to be the most promising animal model to study potential mechanisms of preeclampsia since reductions in uteroplacental blood flow in a variety of animal models lead to a hypertensive state that closely resembles preeclampsia in women. This chapter details the methods we use in our laboratory to produce the reduced uterine perfusion pressure (RUPP) model in the pregnant rat.
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- 2006
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