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Eriksson, Ulf J.
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Publications (10 of 19) Show all publications
Comasco, E., Rangmar, J., Eriksson, U. J. & Oreland, L. (2017). Neurological and neuropsychological effects of low and moderate prenatal alcohol exposure. Acta Physiologica, 222(1), Article ID e12892.
Open this publication in new window or tab >>Neurological and neuropsychological effects of low and moderate prenatal alcohol exposure
2017 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 222, no 1, article id e12892Article in journal (Refereed) Published
Abstract [en]

Several explanations for the diverse results in research on foetal alcohol spectrum disorders or alcohol-related neurodevelopmental disorder might be at hand: timing, amount and patterns of alcohol exposure, as well as complex epigenetic responses. The genetic background of the offspring and its interaction with other prenatal and post-natal environmental cues are likely also of importance. In the present report, key findings about the possible effects of low and moderate doses of maternal alcohol intake on the neuropsychological development of the offspring are reviewed and plausible mechanisms discussed. Special focus is put on the serotonergic system within developmental and gene-environment frameworks. The review also suggests guidelines for future studies and also summarizes some of to-be-answered questions of relevance to clinical practice. Contradictory findings and paucity of studies on the effects of exposure to low alcohol levels during foetal life for the offspring's neuropsychological development call for large prospective studies, as well as for studies including neuroimaging and multi-omics analyses to dissect the neurobiological underpinnings of alcohol exposure-related phenotypes and to identify biomarkers. Finally, it remains to be investigated whether any safe threshold of alcohol drinking during pregnancy can be identified.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
Keywords
alcohol, development, epigenetics, gene, pregnancy, prenatal
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-330918 (URN)10.1111/apha.12892 (DOI)000419864000007 ()28470828 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2011-0627Swedish Research Council, 2009-3640 2015-00495AFA Insurance, SA-07:03EU, European Research Council, INCA 600398
Available from: 2017-10-06 Created: 2017-10-06 Last updated: 2018-05-31Bibliographically approved
Ejdesjö, A., Brings, S., Fleming, T., Fred, R. G., Nawroth, P. P. & Eriksson, U. J. (2016). Receptor for Advanced Glycation End products (RAGE) knockout reduces fetal dysmorphogenesis in murine diabetic pregnancy. Reproductive Toxicology, 62, 62-70
Open this publication in new window or tab >>Receptor for Advanced Glycation End products (RAGE) knockout reduces fetal dysmorphogenesis in murine diabetic pregnancy
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2016 (English)In: Reproductive Toxicology, ISSN 0890-6238, E-ISSN 1873-1708, Vol. 62, p. 62-70Article in journal (Other academic) Published
Abstract [en]

Background & Aim: The receptor for Advanced Glycation End products (RAGE) is implicated in the pathogenesis of diabetic complications, but its importance for the induction of congenital malformations in diabetic pregnancy is unclear. The aim of the present study was to investigate a possible role of RAGE activation in the induction of diabetic embryopathy.

Methods: Female non-diabetic and diabetic wildtype (WT) C57Bl/6 mice and RAGE knockout C57Bl/6 (RAGE‑/-) mice were mated with males of the same genotype. Diabetes was induced by daily streptozotocin (STZ) injections (50 mg/kg STZ i.p.) on five consecutive days. On gestational day 18, pregnant mice were anesthetized and blood was drawn from the heart to measure maternal metabolic parameters. Fetuses and placentas were excised, weighed, and examined for morphological anomalies, and fetal livers were analyzed for 8‑iso‑PGF levels.

Results: There were no malformations in non-diabetic WT or non-diabetic RAGE‑/- mice. However, resorption rates were higher in non-diabetic WT (10%) than in non-diabetic RAGE‑/- mice (4%). Diabetic WT mice had higher malformation (22%) and resorption (43%) rates than diabetic RAGE‑/- mice (3% malformations and 21% resorptions). Maternal diabetes decreased fetal weight more in WT fetuses (44%) than in RAGE‑/- fetuses (36%). There were no differences in plasma glucose levels between the diabetic WT and RAGE‑/- mice, but plasma levels of triglycerides and cholesterol were lower in diabetic WT mice than in diabetic RAGE-/- mice. Diabetes increased maternal plasma levels of methylglyoxal in WT and RAGE‑/- mice, and increased fetal hepatic levels of 8-iso-PGF in WT fetuses, but not in RAGE‑/- fetuses.

Discussion: Knockout of RAGE diminished the rates of fetal malformations and resorptions, despite similar levels of hyperglycemia in pregnant diabetic mice. An anti-teratogenic effect was present in RAGE‑/- mice despite having a more severe diabetic state than diabetic WT mice. As 8-iso-PGF, a marker of oxidative stress, only increased in diabetic WT offspring, this suggested a pivotal role of RAGE activation and oxidative stress in the pathogenesis of diabetic embryopathy.

Keywords
Diabetes; AGE; RAGE; Oxidative stress; Diabetic embryopathy; Neural tube defects; Experimental teratology
National Category
Cell and Molecular Biology
Research subject
Medical Cell Biology
Identifiers
urn:nbn:se:uu:diva-178170 (URN)10.1016/j.reprotox.2016.04.015 (DOI)000378367700008 ()27109771 (PubMedID)
Funder
Swedish Diabetes AssociationNovo NordiskSwedish Research Council, 54X-21117German Research Foundation (DFG), SFB1118
Available from: 2012-07-30 Created: 2012-07-30 Last updated: 2018-01-12Bibliographically approved
Eriksson, U. J. & Wentzel, P. (2016). The status of diabetic embryopathy. Upsala Journal of Medical Sciences, 121(2), 96-112
Open this publication in new window or tab >>The status of diabetic embryopathy
2016 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 121, no 2, p. 96-112Article, review/survey (Refereed) Published
Abstract [en]

Diabetic embryopathy is a theoretical enigma and a clinical challenge. Both type 1 and type 2 diabetic pregnancy carry a significant risk for fetal maldevelopment, and the precise reasons for the diabetes induced teratogenicity are not clearly identified. The experimental work in this field has revealed a partial, however complex, answer to the teratological question, and we will review some of the latest suggestions.

Keywords
Anomalies, development, diabetes in pregnancy, epigenetics, gene expression, malformations
National Category
Endocrinology and Diabetes Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-299776 (URN)10.3109/03009734.2016.1165317 (DOI)000376695600005 ()27117607 (PubMedID)
Funder
Swedish Research CouncilNovo NordiskSwedish Diabetes Association
Available from: 2016-07-27 Created: 2016-07-27 Last updated: 2017-11-28Bibliographically approved
Ejdesjö, A., Wentzel, P. & Eriksson, U. J. (2012). Influence of maternal metabolism and parental genetics on fetal maldevelopment in diabetic rat pregnancy. American Journal of Physiology. Endocrinology and Metabolism, 302(10), E1198-E1209
Open this publication in new window or tab >>Influence of maternal metabolism and parental genetics on fetal maldevelopment in diabetic rat pregnancy
2012 (English)In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 302, no 10, p. E1198-E1209Article in journal (Refereed) Published
Abstract [en]

The purpose of this study was to investigate the influence of parental transgenerational genetics and maternal metabolic state on fetal maldevelopment in diabetic rat pregnancy. Rats from an inbred malformation-resistant (W) strain, and an inbred malformation-prone (L) strain, were cross-mated to produce two different F-1 hybrids, WL and LW. Normal (N) and manifestly diabetic (MD) WL and LW females were mated with normal males of the same F1 generation to obtain WLWL and LWLW F-2 hybrids. Maternal diabetes increased malformation and resorption rates in both F-2 generations. MD-WLWL offspring had higher resorption rate but similar malformation rate compared with the MD-LWLW offspring. Malformed MD-WLWL offspring presented with 100% agnathia/micrognathia, whereas malformed MD-LWL offspring had 60% agnathia/micrognathia and 40% cleft lip and palate. The MD-WL dams showed increased beta-hydroxy-butyrate levels and alterations in concentrations of several amino acids (taurine, asparagine, citrulline, cystine, glutamic acid, leucine, tyrosine, and tryptophan) compared with MD-LW dams. Fetal glyceraldehyde-3-phosphate dehydrogenase (Gapdh) activity and gene expression were more altered in MD-WLWL than MD-LWLW. Fetal gene expression of reactive oxygen species (ROS) scavenger enzymes was diminished in MD-WLWL compared with MD-LWLW. Glial cell line-derived neurotrophic factor and Ret proto-oncogene gene expression was decreased in both MD-WLWL and MD-LWLW fetuses, whereas increased bone morphogenetic protein 4 and decreased Sonic hedgehog homolog expression was found only in MD-LWLW fetuses. Despite identical autosomal genotypes, the WL and LW dams gave birth to offspring with markedly different malformation patterns. Together with fetal differences in enzymatic activity and expression of Gapdh, ROS scavengers, and developmental genes, these results may suggest a teratological mechanism in diabetic pregnancy influenced by maternal metabolism and parental strain epigenetics.

Keywords
diabetes, malformations, teratogenic, gene expression
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-176242 (URN)10.1152/ajpendo.00661.2011 (DOI)000304360400005 ()
Available from: 2012-06-19 Created: 2012-06-18 Last updated: 2017-12-07Bibliographically approved
Nordquist, N., Luthman, H., Pettersson, U. & Eriksson, U. J. (2012). Linkage study of embryopathy-Polygenic inheritance of diabetes-induced skeletal malformations in the rat. Reproductive Toxicology, 33(3), 297-307
Open this publication in new window or tab >>Linkage study of embryopathy-Polygenic inheritance of diabetes-induced skeletal malformations in the rat
2012 (English)In: Reproductive Toxicology, ISSN 0890-6238, E-ISSN 1873-1708, Vol. 33, no 3, p. 297-307Article in journal (Refereed) Published
Abstract [en]

We developed an inbred rat model of diabetic embryopathy, in which the offspring displays skeletal malformations (agnathia or micrognathia) when the mother is diabetic, and no malformations when she is not diabetic. Our aim was to find genes controlling the embryonic maldevelopment in a diabetic environment.

We contrasted the fetal outcome in inbred Sprague-Dawley L rats (20% skeletal malformations in diabetic pregnancy) with that of inbred Wistar Furth rats (denoted W, no skeletal malformations in diabetic pregnancy). We used offspring from the backcross F-1 x L to probe for the genetic basis for malformation of the mandible in diabetic pregnancy. A set of 186 fetuses (93 affected, 93 unaffected) was subjected to a whole genome scan with 160 micro satellites. Analysis of genotype distribution indicated 7 loci on chromosome 4, 10 (3 loci), 14, 18, and 19 in the teratogenic process (and 14 other loci on 12 chromosomes with less strong association to the malformations), several of which contained genes implicated in other experimental studies of diabetic embryopathy. These candidate genes will be scrutinized in further experimentation.

We conclude that the genetic involvement in rodent diabetic embryopathy is polygenic and predisposing for congenital malformations.

Keywords
Rat, Diabetes-in-pregnancy, Streptozotocin, Congenital anomalies, Mandible, Whole genome scan, Micro satellites, Genetic predisposition
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-174683 (URN)10.1016/j.reprotox.2011.12.009 (DOI)000303361200005 ()
Available from: 2012-05-28 Created: 2012-05-25 Last updated: 2017-12-07Bibliographically approved
Wentzel, P. & Eriksson, U. J. (2011). Altered Gene Expression in Rat Cranial Neural Crest Cells Exposed to a Teratogenic Glucose Concentration In Vitro: Paradoxical Downregulation of Antioxidative Defense Genes. Birth defects research. Part B. Developmental and reproductice toxicology, 92(5), 487-497
Open this publication in new window or tab >>Altered Gene Expression in Rat Cranial Neural Crest Cells Exposed to a Teratogenic Glucose Concentration In Vitro: Paradoxical Downregulation of Antioxidative Defense Genes
2011 (English)In: Birth defects research. Part B. Developmental and reproductice toxicology, ISSN 1542-9733, E-ISSN 1542-9741, Vol. 92, no 5, p. 487-497Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Diabetic pregnancy is associated with increased risk of malformation in the infant. Diabetes-induced anomalies of the face and heart are strongly correlated with neural crest cell (NCC) maldevelopment. We aimed to study glucose-induced alterations of mRNA levels in cranial and trunk NCCs isolated from rat embryos with increased risk of developing mandibular and cardiac malformations in diabetic pregnancy.

METHODS: Inbred Sprague-Dawley rat embryos were used for NCC isolation from neural tube explants. The migrating cells were exposed to 5.5 or 30mmol/l glucose concentration for 48 hr, harvested, and prepared for gene expression measurement by RT-PCR or immunostaining with either distal-less (Dlx) or AP-2-alpha antibodies.

RESULTS: Evaluation of the immunostained slides showed that approximately 75% of the cells were of NCC origin. Exposure to 30 mM glucose decreased mRNA levels of Copper-Zinc superoxide dismutase, manganese superoxide dismutase, extracellular superoxide dismutase, Catalase, Gpx-1, Nrf2, poly-ADP ribose polymerase, B-cell leukemia/lymphoma protein 2, and beta-Catenin genes in cranial neural crest explant cultures. In addition, Pax-3, Pax-6, Wnt3a, and Apc mRNA levels were decreased by high glucose exposure in both cranial and trunk neural crest explant cultures.

CONCLUSION: Cranial NCCs diminish their mRNA levels of antioxidative enzymes and the Nrf2 response factor, as well as the antiapoptotic B-cell leukemia/lymphoma protein 2 gene, in response to increased ambient glucose concentration. Furthermore, both cranial and trunk NCC decrease the mRNA levels of the transcription factors Pax-3 and Pax-6, as well as key components of the Wnt pathway. These patterns of glucose-altered gene expression in a developmentally important cell population may be of etiological importance for NCC-associated malformations in diabetic pregnancy.

Keywords
rat, neural crest cells, glucose, gene expression, antioxidative enzymes
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-164441 (URN)10.1002/bdrb.20321 (DOI)000296612100009 ()
Available from: 2011-12-20 Created: 2011-12-20 Last updated: 2017-12-08Bibliographically approved
Ejdesjö, A., Wentzel, P. & Eriksson, U. J. (2011). Genetic and environmental influence on diabetic rat embryopathy. American Journal of Physiology. Endocrinology and Metabolism, 300(3), E454-E467
Open this publication in new window or tab >>Genetic and environmental influence on diabetic rat embryopathy
2011 (English)In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 300, no 3, p. E454-E467Article in journal (Refereed) Published
Abstract [en]

We assessed genetic and environmental influence on fetal outcome in diabetic rat pregnancy. Crossing normal (N) and manifestly diabetic (MD) Wistar Furth (W) and Sprague-Dawley (L) females with W or L males yielded 4 different fetal genotypes (WW, LL, WL, LW) in N or MD rat pregnancies for studies. We also evaluated fetal outcome in litters with enhanced or diminished severity of maternal MD state, denoted MD(+)WL and MD(-)LW. The MDWW litters had less malformations and resorptions (0% and 19%) than the MDLL litters (17% and 30%). The MDWL litters (0% and 8%) were less maldeveloped than the MDLW litters (9% and 22%), whereas the MD(+)WL (3% and 23%) and MD(-)LW (1% and 17%) litters showed increased and decreased dysmorphogenesis (compared to MDWL and MDLW litters). The pregnant MDW rats had lower serum levels of glucose, fructosamine and branched chain amino acids than the pregnant MDL rats, whereas the pregnant MD(+)W and MD(-)L rats had levels comparable to those of the MDL and MDW rats, respectively. The 8-iso-PGF2α levels of the malformed MDLW offspring were increased compared to the non-malformed MDLW offspring. Diabetes decreased fetal heart Ret and increased Bmp-4 gene expression in the MDLW offspring, and caused decreased GDNF and Shh expression in the malformed fetal mandible of the MDLW offspring. We conclude that the fetal (epi)genome controls the embryonic dysmorphogenesis in diabetic pregnancy by instigating a threshold level for the teratological insult, and that the maternal genome controls the teratogenic insult by (dys)regulating the maternal metabolism.

Keywords
diabetes in pregnancy, congenital abnormalities, teratology, animal experimentation, aldose reductase, glyceraldehyde-3-phosphate dehydrogenase, sonic hedgehog homologue, ret proto-oncogene, glial-derived neurotrophic factor, antioxidative enzymes
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-105013 (URN)10.​1152/​ajpendo.​00543.​2010 (DOI)000287796200004 ()21119026 (PubMedID)
Available from: 2009-05-31 Created: 2009-05-31 Last updated: 2017-12-13Bibliographically approved
Wikström, A.-K., Larsson, A., Eriksson, U. J., Nash, P. & Olovsson, M. (2008). Early postpartum changes in circulating pro- and anti-angiogenic factors in early-onset and late-onset pre-eclampsia. Acta Obstetricia et Gynecologica Scandinavica, 87(2), 146-153
Open this publication in new window or tab >>Early postpartum changes in circulating pro- and anti-angiogenic factors in early-onset and late-onset pre-eclampsia
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2008 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 87, no 2, p. 146-153Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Pre-eclampsia is associated with altered plasma concentrations of the pro- and anti-angiogenic factors placental growth factor (PlGF), vascular endothelial growth factor-A (VEGF-A) and soluble fms-like tyrosine kinase 1 (sFlt1). However, there is insufficient knowledge about how these concentrations change after delivery, and whether the changes differ between early-onset and late-onset pre-eclampsia. METHODS: Plasma concentrations of sFlt1, PlGF and VEGF-A were measured before delivery and on days 1, 3 and 7 postpartum in women with early-onset (24-32 weeks' gestation) (n=18) and late-onset pre-eclampsia (35-42 weeks' gestation) (n=20) and in control groups delivered in corresponding weeks of gestation. RESULTS: All groups showed a rapid decrease in median sFlt1 concentration postpartum. Women with late-onset pre-eclampsia did not differ in sFlt1 concentration from controls on day 1 postpartum, whereas women with early-onset pre-eclampsia displayed a persistently elevated sFlt1 concentration on day 7 postpartum compared with controls. PlGF concentrations did not change from before delivery to any time point postpartum in the pre-eclampsia groups. VEGF-A concentrations were slightly increased on day 7 postpartum in both pre-eclampsia and control groups compared to concentrations prior to delivery. CONCLUSION: Median sFlt1 concentrations decreased rapidly postpartum in all groups, but remained higher in early-onset pre-eclampsia than controls on day 7. Postpartum, the median PlGF concentrations were similar to the concentrations measured before delivery in women with pre-eclampsia.

Keywords
preeclampsia, angiogenesis, sFlt-1
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-104590 (URN)10.1080/00016340701819262 (DOI)000252762000003 ()18231881 (PubMedID)
Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2017-12-13Bibliographically approved
Wentzel, P. & Eriksson, U. J. (2008). Genetic influence on dysmorphogenesis in embryos from different rat strains exposed to ethanol in vivo and in vitro. Alcoholism: Clinical and Experimental Research, 32(5), 874-887
Open this publication in new window or tab >>Genetic influence on dysmorphogenesis in embryos from different rat strains exposed to ethanol in vivo and in vitro
2008 (English)In: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 32, no 5, p. 874-887Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The aim was to investigate the susceptibility of embryos from 2 rat strains (U and H) to a 48 hours ethanol exposure in early pregnancy, both in vivo and in vitro. METHODS: The embryos were studied on gestational days 9 to 11. We used 1 ethanol dose in vivo (6 g/kg x 2), 3 different ethanol concentrations in vitro (88 mM, 132 mM, 176 mM) and also attempted to diminish the teratogenic effect in vitro by supplying the antioxidant N-acetylcysteine (NAC, 0.5 mM) to the culture medium. RESULTS: The U embryos were more damaged by ethanol than the H embryos, both in vivo and in vitro. NAC addition diminished, but failed to completely normalize, the embryonic maldevelopment. Ethanol increased the Bax/Bcl-2 ratio in the U embryos both in vivo and in vitro, but not in the H embryos. Furthermore, ethanol caused increased Caspase-3 immunostaining in U embryos, but not in H embryos. Ethanol exposure in vivo did not alter CuZnSOD and MnSOD mRNA levels in U and H embryos. In vitro, however, the ethanol-exposed U embryos increased their CuZnSOD and MnSOD mRNA levels, whereas the CuZnSOD mRNA was unchanged and MnSOD mRNA decreased in the H embryos, in neither strain did NAC exert any effect. The U embryos increased catalase gene expression in response to ethanol in vivo, but decreased catalase mRNA levels in vitro, changes normalized by NAC. The H embryos did not alter catalase mRNA levels in vivo, but increased gene expression in vitro, with no NAC effect. Ethanol affected the gene expression of the other ROS scavenging enzymes and the developmental genes studied - Bmp-4, Ret, Shh, Pax-6 - similarly in the 2 strains. CONCLUSIONS: The findings support a role for genetic predisposition, oxidative stress, and apoptosis in ethanol teratogenicity, and suggest that the teratogenic predisposition of the more susceptible U rats may reside, at least in part, in the regulation of the ROS scavenging enzymes in the U embryos.

Keywords
rat, ethanol, pregnancy, embryo, congenital anomalies
National Category
Cell and Molecular Biology
Research subject
Medical Cell Biology
Identifiers
urn:nbn:se:uu:diva-104963 (URN)10.1111/j.1530-0277.2008.00647.x (DOI)000255598000020 ()
Available from: 2009-05-31 Created: 2009-05-31 Last updated: 2018-01-13Bibliographically approved
Carlström, M., Lai, E. Y., Steege, A., Sendeski, M., Ma, Z., Zabihi, S., . . . Persson, A. E. (2008). Nitric oxide deficiency and increased adenosine response of afferent arterioles in hydronephrotic mice with hypertension. Hypertension, 51(5), 1386-1392
Open this publication in new window or tab >>Nitric oxide deficiency and increased adenosine response of afferent arterioles in hydronephrotic mice with hypertension
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2008 (English)In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 51, no 5, p. 1386-1392Article, review/survey (Refereed) Published
Abstract [en]

Afferent arterioles were used to investigate the role of adenosine, angiotensin II, NO, and reactive oxygen species in the pathogenesis of increased tubuloglomerular feedback response in hydronephrosis. Hydronephrosis was induced in wild-type mice, superoxide dismutase-1 overexpressed mice (superoxide-dismutase-1 transgenic), and deficient mice (superoxide dismutase-1 knockout). Isotonic contractions in isolated perfused arterioles and mRNA expression of NO synthase isoforms, adenosine, and angiotensin II receptors were measured. In wild-type mice, N(G)-nitro-L-arginine methyl ester (L-NAME) did not change the basal arteriolar diameter of hydronephrotic kidneys (-6%) but reduced it in control (-12%) and contralateral arterioles (-43%). Angiotensin II mediated a weaker maximum contraction of hydronephrotic arterioles (-18%) than in control (-42%) and contralateral arterioles (-49%). The maximum adenosine-induced constriction was stronger in hydronephrotic (-19%) compared with control (-8%) and contralateral kidneys (+/-0%). The response to angiotensin II became stronger in the presence of adenosine in hydronephrotic kidneys and attenuated in contralateral arterioles. L-NAME increased angiotensin II responses of all of the groups but less in hydronephrotic kidneys. The mRNA expression of endothelial NO synthase and inducible NO synthase was upregulated in the hydronephrotic arterioles. No differences were found for adenosine or angiotensin II receptors. In superoxide dismutase-1 transgenic mice, strong but similar L-NAME response (-40%) was observed for all of the groups. This response was totally abolished in arterioles of hydronephrotic superoxide dismutase-1 knockout mice. In conclusion, hydronephrosis is associated with changes in the arteriolar reactivity of both hydronephrotic and contralateral kidneys. Increased oxidative stress, reduced NO availability, and stronger reactivity to adenosine of the hydronephrotic kidney may contribute to the enhanced tubuloglomerular feedback responsiveness in hydronephrosis and be involved in the development of hypertension.

Place, publisher, year, edition, pages
American Heart Association, 2008
Keywords
angiotensin II, L-NAME, oxidative stress, NO synthase, superoxide dismutase, tubuloglomerular feedback
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-104329 (URN)10.1161/HYPERTENSIONAHA.108.111070 (DOI)000255016500024 ()18391091 (PubMedID)
Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2017-12-13Bibliographically approved
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