Gravidez e nefrotoxidade causada pela ciclosporina A: um estudo experimental

Detalhes bibliográficos
Autor(a) principal: Mendes, Glória Elisa Florido
Data de Publicação: 2005
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da FAMERP
Texto Completo: http://bdtd.famerp.br/handle/tede/217
Resumo: Cyclosporine A (CsA) is a immunosuppressant drug, whose most serious toxic effect is chronic nephrotoxicity, characterized by decreased glomerular filtration rate and the development of irreversible renal fibrosis. It may go through the placenta to the developing fetus. Currently, a great number of women with childbearing potential is treated by CsA, increasing the chances of pregnancy under the effect of this drug. Our objectives were to assess CsA effects on the renal structure and function during pregnancy. The low-salt-diet (0.06%) model was used in pregnant (P/CsA) and virgin (V/CsA) Munich-Wistar female rats receiving CsA; in virgin (V/VH) and pregnant (P/VH) rats with vehicle at a dosage of 15 mg/kg/day of CsA subcutaneously or vehicle. Glomerular filtration rate (GFR, ml/min/100g) , renal blood flow (RBF, Doppler ultrasound, ml/min), renal vascular resistance (RVR, mmHg/ml/min), blood pressure (BP, intracarotid probe, mmHg), blood levels of CsA (BCsA, radioimmunoassay, ng/ml), urinary volume (UV, ml/min), plasma and urinary creatinine (mg/dl), urine sodium excretion (UNa, mEq/l), sodium excretion fraction (FeNa,%) urinary osmolality (UOsm, m/Osm/K), osmolar clearance (COsm, ml/min), urinary nitric-oxide (NO, griess, umol/mgCr), immunohistochemistry for angiotensin II-positive renal cells and renal histology were measured in the middle and at the end of the gestational period (21 days). Results are presented as mean ± standard error of mean and analyzed by ANOVA and Student-Neuman-Keuls test. After 10 days of treatment, the pregnancy caused significant increases of 27% in the GFR (GC; 1.19 ± 0.04 vs 0.94 ± 0.05 in V/C, p<0.05) and of 36% in RBF (G/C; 4.9 ± 0.2 vs 3.6 ± 0.1 in V/C, p< 0.001) and significant decreases of 13% in MBP (GC; 112 ± 4 vs 129 ± 5 in V/C, p<0.05) and of 29% in RVR ( GC; 24 ± 1 vs 34 ± 2 in VC, p<0.05) of vehicle treated animals. In contrast, in CsA-treated animals, there was no significant GFR increase in pregnancy (20%, G/CsA; 0.95 ± 0.07 vs 0.79 ± 0.07 in V/CsA, p>0.05) nor was there a significant MPB decrease (7%, G/CsA; 110 ± 3 vs 118 ± 4 in V/CsA, p>0.05). The significant RBF increase (38%, G/CsA; 3.3 ± 0.2 vs 2.4 ± 0.1 in V/CsA p<0,01) and significant RVR decrease ( 24%, G/CsA 38 ± 3 vs 50 ± 3 in V/CsA, p<0.05) were maintained in this group. Pregnancy caused a significant decrease of CsA serum levels (G/CsA; 544±58 vs 805±71 in V/CsA, p<0.01). CsA treated animals showed a trend to higher urinary nitric oxide levels, however, the difference was not statistically significant. There was no difference in urinary nitric oxide between virgin and pregnant rats. Pregnancy increased the number of angiotensin II-positive cells in the renal interstitium (3.9 ± 0.6 in G/CsA vs 2.5 ± 0.4 in V/CsA and 4 ± 1.4 in G/C vs 1.9 ± 0.86 in V/C), however these differences did not reach statistical significance. The number of angiotensin II-positive cells in the afferent arteriole was greater in pregnant rats when compared to virgin rats (G/C; 1.3 ± 0.3 vs 0.21 ± 0.2 in V/C) and greater in CsA-treated virgin rats when compared to vehicle-treated rats (V/CsA; 1 ± 0.3 vs 0.21 ± 0.2 in V/C), however these differences were not statistically significant. After 20 days, V and P rats had similar (NS) GFR and RBF decreases and CsA vs Control for GFR (p<0.001), for RBF (p<0.01), and a similar RVR increase (NS). MBP values showed similar decreases in V vs P rats (NS) and a decrease in Csa vs C animals (p<0.05). SCsA was lower in P vs V rats (p<0.001). AII expression in the interstice increased for V/CsA vs V/C rats (p<0.001) and for G/CsA vs P/C rats (p<0.05). The same was observed in the afferent arteriole, for V/CsA vs v/C (p<0.01); however it was not statistically significant for pregnant rats. Only the V/CsA group had an IF score of 0.2 ± 0.1 after 20 days. In the middle of normal pregnancy, CsA altered the renal hemodynamics, impairing both the increase of GFR and the decrease of BP, although the blood levels of the drug were lower in pregnant rats than in virgin rats. The NO urinary system does not seem to be connected to this phenomenon. AII expression in the interstice and in the afferent arteriole was greater for CsA treated-pregnant animals vs controls. Pregnancy did not impair CsA-induced interstitial fibrosis.
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spelling Burdmann, Emmanuel de AlmeidaCPF:01180433823http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4793969P6&dataRevisao=nullVieira Júnior, José MauroCPF:95704221734http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4769753T8&dataRevisao=nullAraújo, Ivan MeloCPF:00000000002http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4721562T6&dataRevisao=nullLima, Emerson Quintino deCPF:00000000003http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4723719T8&dataRevisao=nullCipullo, José PauloCPF:01892789868http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4779373J2&dataRevisao=nullCPF:05225559859http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4779021D6&dataRevisao=nullMendes, Glória Elisa Florido2016-01-26T12:51:50Z2006-07-042005-11-28MENDES, Glória Elisa Florido. Gravidez e nefrotoxidade causada pela ciclosporina A: um estudo experimental. 2005. 103 f. Tese (Doutorado em Medicina Interna; Medicina e Ciências Correlatas) - Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, 2005.http://bdtd.famerp.br/handle/tede/217Cyclosporine A (CsA) is a immunosuppressant drug, whose most serious toxic effect is chronic nephrotoxicity, characterized by decreased glomerular filtration rate and the development of irreversible renal fibrosis. It may go through the placenta to the developing fetus. Currently, a great number of women with childbearing potential is treated by CsA, increasing the chances of pregnancy under the effect of this drug. Our objectives were to assess CsA effects on the renal structure and function during pregnancy. The low-salt-diet (0.06%) model was used in pregnant (P/CsA) and virgin (V/CsA) Munich-Wistar female rats receiving CsA; in virgin (V/VH) and pregnant (P/VH) rats with vehicle at a dosage of 15 mg/kg/day of CsA subcutaneously or vehicle. Glomerular filtration rate (GFR, ml/min/100g) , renal blood flow (RBF, Doppler ultrasound, ml/min), renal vascular resistance (RVR, mmHg/ml/min), blood pressure (BP, intracarotid probe, mmHg), blood levels of CsA (BCsA, radioimmunoassay, ng/ml), urinary volume (UV, ml/min), plasma and urinary creatinine (mg/dl), urine sodium excretion (UNa, mEq/l), sodium excretion fraction (FeNa,%) urinary osmolality (UOsm, m/Osm/K), osmolar clearance (COsm, ml/min), urinary nitric-oxide (NO, griess, umol/mgCr), immunohistochemistry for angiotensin II-positive renal cells and renal histology were measured in the middle and at the end of the gestational period (21 days). Results are presented as mean ± standard error of mean and analyzed by ANOVA and Student-Neuman-Keuls test. After 10 days of treatment, the pregnancy caused significant increases of 27% in the GFR (GC; 1.19 ± 0.04 vs 0.94 ± 0.05 in V/C, p<0.05) and of 36% in RBF (G/C; 4.9 ± 0.2 vs 3.6 ± 0.1 in V/C, p< 0.001) and significant decreases of 13% in MBP (GC; 112 ± 4 vs 129 ± 5 in V/C, p<0.05) and of 29% in RVR ( GC; 24 ± 1 vs 34 ± 2 in VC, p<0.05) of vehicle treated animals. In contrast, in CsA-treated animals, there was no significant GFR increase in pregnancy (20%, G/CsA; 0.95 ± 0.07 vs 0.79 ± 0.07 in V/CsA, p>0.05) nor was there a significant MPB decrease (7%, G/CsA; 110 ± 3 vs 118 ± 4 in V/CsA, p>0.05). The significant RBF increase (38%, G/CsA; 3.3 ± 0.2 vs 2.4 ± 0.1 in V/CsA p<0,01) and significant RVR decrease ( 24%, G/CsA 38 ± 3 vs 50 ± 3 in V/CsA, p<0.05) were maintained in this group. Pregnancy caused a significant decrease of CsA serum levels (G/CsA; 544±58 vs 805±71 in V/CsA, p<0.01). CsA treated animals showed a trend to higher urinary nitric oxide levels, however, the difference was not statistically significant. There was no difference in urinary nitric oxide between virgin and pregnant rats. Pregnancy increased the number of angiotensin II-positive cells in the renal interstitium (3.9 ± 0.6 in G/CsA vs 2.5 ± 0.4 in V/CsA and 4 ± 1.4 in G/C vs 1.9 ± 0.86 in V/C), however these differences did not reach statistical significance. The number of angiotensin II-positive cells in the afferent arteriole was greater in pregnant rats when compared to virgin rats (G/C; 1.3 ± 0.3 vs 0.21 ± 0.2 in V/C) and greater in CsA-treated virgin rats when compared to vehicle-treated rats (V/CsA; 1 ± 0.3 vs 0.21 ± 0.2 in V/C), however these differences were not statistically significant. After 20 days, V and P rats had similar (NS) GFR and RBF decreases and CsA vs Control for GFR (p<0.001), for RBF (p<0.01), and a similar RVR increase (NS). MBP values showed similar decreases in V vs P rats (NS) and a decrease in Csa vs C animals (p<0.05). SCsA was lower in P vs V rats (p<0.001). AII expression in the interstice increased for V/CsA vs V/C rats (p<0.001) and for G/CsA vs P/C rats (p<0.05). The same was observed in the afferent arteriole, for V/CsA vs v/C (p<0.01); however it was not statistically significant for pregnant rats. Only the V/CsA group had an IF score of 0.2 ± 0.1 after 20 days. In the middle of normal pregnancy, CsA altered the renal hemodynamics, impairing both the increase of GFR and the decrease of BP, although the blood levels of the drug were lower in pregnant rats than in virgin rats. The NO urinary system does not seem to be connected to this phenomenon. AII expression in the interstice and in the afferent arteriole was greater for CsA treated-pregnant animals vs controls. Pregnancy did not impair CsA-induced interstitial fibrosis.A ciclosporina A (CsA) é uma droga imunossupressora cujo efeito tóxico mais grave é a nefrotoxicidade, caracterizada pela queda da filtração glomerular e pelo desenvolvimento de fibrose intersticial renal irreversível. A CsA pode passar através da placenta para o feto em desenvolvimento. Atualmente, um grande número de mulheres em idade fértil são tratadas com CsA, aumentando a chance de gestação sob efeito desta droga. Os objetivos deste estudo foram avaliar os efeitos da CsA sobre a função e estrutura renal durante a gravidez. Utilizou-se o modelo da manobra de restrição de sal na dieta (0,06%) em ratas Munich-Wistar, virgens que receberam CsA (V/CsA), grávidas com CsA (G/CsA), virgens com veículo (V/C) e grávidas com veículo (GIC), na dose de 15 mg/Kg/dia de CsA subcutâneo ou veículo. Avaliou-se na metade e no final do período gestacional a filtração glomerular (FGR, depuração de inulina, ml/min/100g), o fluxo sanguíneo renal (FSR, ultra-som Doppler, ml/min), a resistência vascular renal (RVR, mmHg/ml/min), a pressão arterial média (PAM, cateter intracarotídeo, mmHg), os níveis sanguíneos de CsA (SCsA, radioimunoensaio, ng/ml), o volume urinário (VU, l/min), a creatinina plasmática e urinária (mg/dl), a excreção urinária de sódio (UNa, mEqIl), a fração de excreção de sódio (FeNa,%), a osmolalidade urinária (Uosm, m/Osm/K), a depuração osmolar (Cosm, ml/min), o óxido nítrico urinário (NO, griess, pmol/mgCr), a imunohistoquímica para células renais positivas para angiotensina II (células/campo) e a histologia renal. Os resultados são apresentados como média erro padrão e comparados por ANOVA e StudentNeuman-Keuls. Após 10 dias de tratamento a gravidez provocou aumentos significantes de 27% na FGR (GC; 1,19 0,04 vs 0,94 0,05 em V/C, p<0,05) e de 36% no FSR (G/C 49 + 0,2 vs 36 + 0,1 em V/C, p< 0,001) e quedas significantes de 13% na PAM (GC; 112 4 vs 129 5 em V/C, p<0,05) e de 29% na RVR (GC; 24 1 vs 34 2 em VC, p<0,05) Nota de Resumo dos animais tratados com veículo. Em contraste, nos animais tratados com CsA, na gravidez não houve aumento significante da FOR (20%, G/CsA; 0,95 + 0,07 vs 0,79 + 0,07 em V/CsA, p>0,05) ou queda significante da PAM (7%, G/CsA; 110 3 vs 118 4 em V/CsA, p>0,05). Neste grupo manteve-se a elevação significante do FSR (38%, G/CsA; 3,3 0,2 vs 2 4 0,1 em V/CsA p<0,01) e a diminuição significante da RVR (24%, C/CsA 38 3 vs 50 3 em V/CsA, p<0,05). A gravidez provocou diminuição significante dos níveis séricos de CsA (G/CsA; 544 58 vs 805 71 em V/CsA, p<0,0 1). Os animais tratados com CsA apresentaram tendência a níveis mais elevados de óxido nítrico urinário, porém a diferença não foi estatisticamente significante. Não houve diferença de óxido nítrico urinário entre ratas virgens e grávidas. A gravidez causou aumento do número de células positivas para angiotensina II no interstício renal (3,90,6 em G/CsA vs 2,5 0,4 em V/CsA e 4 1,4 em C/C vs 1,9 0,86 em V/C), porém estas diferenças não alcançaram signíficância estatística. O número de células positivas para angiotensina li na arteríola aferente foi maior nas ratas grávidas quando comparadas às virgens (G/C; 1,3 0,3 vs O 21 + O 2 em V/C) e maior nas ratas virgens tratadas com CsA quando comparadas às tratadas com veículo (V/CsA 1 + 0,3 vs 021 + 02 em V/C), porém, estas diferenças não foram estatisticamente significantes. Após 20 dias, V e O apresentaram queda similares (NS) na FGR e FSR, sendo CsA vs Controle para FGR (p<0.001), para FSR (p<0.01), e aumentando similar na RVR (NS). Os valores da PAM apresentaram quedas similares, em V vs G (NS) e diminuição nos animais com CsA vs C (p<0,05). A SCsA foi menor em G vs V (p<0,01). A expressão de AII no interstício aumentou, para V/CsA vs V/C (p<0,001) e para G/CsA vs G/C (p<0,05). O mesmo aconteceu na arteríola aferente, para V/CsA vs V/C (p<0,01); todavia não foi estatisticamente significante para as ratas prenhes. Nota de Resumo Apenas o grupo V/CsA após 20 dias apresentou escore de 0,2 + 0,1 de IRF. A CsA alterou desfavoravelmente a hemodinâmica renal na metade da gravidez normal, prejudicando o aumento da FGR e prejudicando queda da PA na prenhez normal, apesar de as ratas prenhes apresentarem níveis sangüíneos da droga menores em relação às virgens. O NO não parece estar envolvido nesse fenômeno. A expressão da AII no interstício e na arteríola aferente foi maior para os animais com CsA e prenhes vs controles. A gravidez não prejudicou a fibrose intersticial causada pela CsA.Made available in DSpace on 2016-01-26T12:51:50Z (GMT). No. of bitstreams: 1 gloriaelisa_tese.pdf: 873601 bytes, checksum: 4169d3e3662f4f5b0cb50f642bec7715 (MD5) Previous issue date: 2005-11-28Conselho Nacional de Desenvolvimento Científico e Tecnológicoapplication/pdfporFaculdade de Medicina de São José do Rio PretoPrograma de Pós-Graduação em Ciências da SaúdeFAMERPBRMedicina Interna; Medicina e Ciências CorrelatasNefrotoxicidadeCiclosporinaGravidezRatosCiclosporinas/toxicidadeNefropatiasCyclosporins/toxicityKidney DiseasesNephrologyNephrotoxicityCyclosporine APregnancyRatsCiclosporinas/toxicidadNefropatíasEmbarazoRatasCNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::NEFROLOGIAGravidez e nefrotoxidade causada pela ciclosporina A: um estudo experimentalinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da FAMERPinstname:Faculdade de Medicina de São José do Rio Preto (FAMERP)instacron:FAMERPORIGINALgloriaelisa_tese.pdfapplication/pdf8736014169d3e3662f4f5b0cb50f642bec7715MD51http://bdtd.famerp.br/bitstream/tede/217/1/gloriaelisa_tese.pdftede/2172019-02-04 11:06:06.639oai:localhost:tede/217Biblioteca Digital de Teses e Dissertaçõeshttp://bdtd.famerp.br/PUBhttps://bdtd.famerp.br/oai/requestsbdc@famerp.br||joao.junior@famerp.bropendoar:47112019-02-04T13:06:06Biblioteca Digital de Teses e Dissertações da FAMERP - Faculdade de Medicina de São José do Rio Preto (FAMERP)false
dc.title.por.fl_str_mv Gravidez e nefrotoxidade causada pela ciclosporina A: um estudo experimental
title Gravidez e nefrotoxidade causada pela ciclosporina A: um estudo experimental
spellingShingle Gravidez e nefrotoxidade causada pela ciclosporina A: um estudo experimental
Mendes, Glória Elisa Florido
Nefrotoxicidade
Ciclosporina
Gravidez
Ratos
Ciclosporinas/toxicidade
Nefropatias
Cyclosporins/toxicity
Kidney Diseases
Nephrology
Nephrotoxicity
Cyclosporine A
Pregnancy
Rats
Ciclosporinas/toxicidad
Nefropatías
Embarazo
Ratas
CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::NEFROLOGIA
title_short Gravidez e nefrotoxidade causada pela ciclosporina A: um estudo experimental
title_full Gravidez e nefrotoxidade causada pela ciclosporina A: um estudo experimental
title_fullStr Gravidez e nefrotoxidade causada pela ciclosporina A: um estudo experimental
title_full_unstemmed Gravidez e nefrotoxidade causada pela ciclosporina A: um estudo experimental
title_sort Gravidez e nefrotoxidade causada pela ciclosporina A: um estudo experimental
author Mendes, Glória Elisa Florido
author_facet Mendes, Glória Elisa Florido
author_role author
dc.contributor.advisor1.fl_str_mv Burdmann, Emmanuel de Almeida
dc.contributor.advisor1ID.fl_str_mv CPF:01180433823
dc.contributor.advisor1Lattes.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4793969P6&dataRevisao=null
dc.contributor.referee1.fl_str_mv Vieira Júnior, José Mauro
dc.contributor.referee1ID.fl_str_mv CPF:95704221734
dc.contributor.referee1Lattes.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4769753T8&dataRevisao=null
dc.contributor.referee2.fl_str_mv Araújo, Ivan Melo
dc.contributor.referee2ID.fl_str_mv CPF:00000000002
dc.contributor.referee2Lattes.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4721562T6&dataRevisao=null
dc.contributor.referee3.fl_str_mv Lima, Emerson Quintino de
dc.contributor.referee3ID.fl_str_mv CPF:00000000003
dc.contributor.referee3Lattes.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4723719T8&dataRevisao=null
dc.contributor.referee4.fl_str_mv Cipullo, José Paulo
dc.contributor.referee4ID.fl_str_mv CPF:01892789868
dc.contributor.referee4Lattes.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4779373J2&dataRevisao=null
dc.contributor.authorID.fl_str_mv CPF:05225559859
dc.contributor.authorLattes.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4779021D6&dataRevisao=null
dc.contributor.author.fl_str_mv Mendes, Glória Elisa Florido
contributor_str_mv Burdmann, Emmanuel de Almeida
Vieira Júnior, José Mauro
Araújo, Ivan Melo
Lima, Emerson Quintino de
Cipullo, José Paulo
dc.subject.por.fl_str_mv Nefrotoxicidade
Ciclosporina
Gravidez
Ratos
Ciclosporinas/toxicidade
Nefropatias
topic Nefrotoxicidade
Ciclosporina
Gravidez
Ratos
Ciclosporinas/toxicidade
Nefropatias
Cyclosporins/toxicity
Kidney Diseases
Nephrology
Nephrotoxicity
Cyclosporine A
Pregnancy
Rats
Ciclosporinas/toxicidad
Nefropatías
Embarazo
Ratas
CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::NEFROLOGIA
dc.subject.eng.fl_str_mv Cyclosporins/toxicity
Kidney Diseases
Nephrology
Nephrotoxicity
Cyclosporine A
Pregnancy
Rats
dc.subject.spa.fl_str_mv Ciclosporinas/toxicidad
Nefropatías
Embarazo
Ratas
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::NEFROLOGIA
description Cyclosporine A (CsA) is a immunosuppressant drug, whose most serious toxic effect is chronic nephrotoxicity, characterized by decreased glomerular filtration rate and the development of irreversible renal fibrosis. It may go through the placenta to the developing fetus. Currently, a great number of women with childbearing potential is treated by CsA, increasing the chances of pregnancy under the effect of this drug. Our objectives were to assess CsA effects on the renal structure and function during pregnancy. The low-salt-diet (0.06%) model was used in pregnant (P/CsA) and virgin (V/CsA) Munich-Wistar female rats receiving CsA; in virgin (V/VH) and pregnant (P/VH) rats with vehicle at a dosage of 15 mg/kg/day of CsA subcutaneously or vehicle. Glomerular filtration rate (GFR, ml/min/100g) , renal blood flow (RBF, Doppler ultrasound, ml/min), renal vascular resistance (RVR, mmHg/ml/min), blood pressure (BP, intracarotid probe, mmHg), blood levels of CsA (BCsA, radioimmunoassay, ng/ml), urinary volume (UV, ml/min), plasma and urinary creatinine (mg/dl), urine sodium excretion (UNa, mEq/l), sodium excretion fraction (FeNa,%) urinary osmolality (UOsm, m/Osm/K), osmolar clearance (COsm, ml/min), urinary nitric-oxide (NO, griess, umol/mgCr), immunohistochemistry for angiotensin II-positive renal cells and renal histology were measured in the middle and at the end of the gestational period (21 days). Results are presented as mean ± standard error of mean and analyzed by ANOVA and Student-Neuman-Keuls test. After 10 days of treatment, the pregnancy caused significant increases of 27% in the GFR (GC; 1.19 ± 0.04 vs 0.94 ± 0.05 in V/C, p<0.05) and of 36% in RBF (G/C; 4.9 ± 0.2 vs 3.6 ± 0.1 in V/C, p< 0.001) and significant decreases of 13% in MBP (GC; 112 ± 4 vs 129 ± 5 in V/C, p<0.05) and of 29% in RVR ( GC; 24 ± 1 vs 34 ± 2 in VC, p<0.05) of vehicle treated animals. In contrast, in CsA-treated animals, there was no significant GFR increase in pregnancy (20%, G/CsA; 0.95 ± 0.07 vs 0.79 ± 0.07 in V/CsA, p>0.05) nor was there a significant MPB decrease (7%, G/CsA; 110 ± 3 vs 118 ± 4 in V/CsA, p>0.05). The significant RBF increase (38%, G/CsA; 3.3 ± 0.2 vs 2.4 ± 0.1 in V/CsA p<0,01) and significant RVR decrease ( 24%, G/CsA 38 ± 3 vs 50 ± 3 in V/CsA, p<0.05) were maintained in this group. Pregnancy caused a significant decrease of CsA serum levels (G/CsA; 544±58 vs 805±71 in V/CsA, p<0.01). CsA treated animals showed a trend to higher urinary nitric oxide levels, however, the difference was not statistically significant. There was no difference in urinary nitric oxide between virgin and pregnant rats. Pregnancy increased the number of angiotensin II-positive cells in the renal interstitium (3.9 ± 0.6 in G/CsA vs 2.5 ± 0.4 in V/CsA and 4 ± 1.4 in G/C vs 1.9 ± 0.86 in V/C), however these differences did not reach statistical significance. The number of angiotensin II-positive cells in the afferent arteriole was greater in pregnant rats when compared to virgin rats (G/C; 1.3 ± 0.3 vs 0.21 ± 0.2 in V/C) and greater in CsA-treated virgin rats when compared to vehicle-treated rats (V/CsA; 1 ± 0.3 vs 0.21 ± 0.2 in V/C), however these differences were not statistically significant. After 20 days, V and P rats had similar (NS) GFR and RBF decreases and CsA vs Control for GFR (p<0.001), for RBF (p<0.01), and a similar RVR increase (NS). MBP values showed similar decreases in V vs P rats (NS) and a decrease in Csa vs C animals (p<0.05). SCsA was lower in P vs V rats (p<0.001). AII expression in the interstice increased for V/CsA vs V/C rats (p<0.001) and for G/CsA vs P/C rats (p<0.05). The same was observed in the afferent arteriole, for V/CsA vs v/C (p<0.01); however it was not statistically significant for pregnant rats. Only the V/CsA group had an IF score of 0.2 ± 0.1 after 20 days. In the middle of normal pregnancy, CsA altered the renal hemodynamics, impairing both the increase of GFR and the decrease of BP, although the blood levels of the drug were lower in pregnant rats than in virgin rats. The NO urinary system does not seem to be connected to this phenomenon. AII expression in the interstice and in the afferent arteriole was greater for CsA treated-pregnant animals vs controls. Pregnancy did not impair CsA-induced interstitial fibrosis.
publishDate 2005
dc.date.issued.fl_str_mv 2005-11-28
dc.date.available.fl_str_mv 2006-07-04
dc.date.accessioned.fl_str_mv 2016-01-26T12:51:50Z
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dc.identifier.citation.fl_str_mv MENDES, Glória Elisa Florido. Gravidez e nefrotoxidade causada pela ciclosporina A: um estudo experimental. 2005. 103 f. Tese (Doutorado em Medicina Interna; Medicina e Ciências Correlatas) - Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, 2005.
dc.identifier.uri.fl_str_mv http://bdtd.famerp.br/handle/tede/217
identifier_str_mv MENDES, Glória Elisa Florido. Gravidez e nefrotoxidade causada pela ciclosporina A: um estudo experimental. 2005. 103 f. Tese (Doutorado em Medicina Interna; Medicina e Ciências Correlatas) - Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, 2005.
url http://bdtd.famerp.br/handle/tede/217
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dc.publisher.none.fl_str_mv Faculdade de Medicina de São José do Rio Preto
dc.publisher.program.fl_str_mv Programa de Pós-Graduação em Ciências da Saúde
dc.publisher.initials.fl_str_mv FAMERP
dc.publisher.country.fl_str_mv BR
dc.publisher.department.fl_str_mv Medicina Interna; Medicina e Ciências Correlatas
publisher.none.fl_str_mv Faculdade de Medicina de São José do Rio Preto
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da FAMERP
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instname_str Faculdade de Medicina de São José do Rio Preto (FAMERP)
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reponame_str Biblioteca Digital de Teses e Dissertações da FAMERP
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repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da FAMERP - Faculdade de Medicina de São José do Rio Preto (FAMERP)
repository.mail.fl_str_mv sbdc@famerp.br||joao.junior@famerp.br
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