Losartan modulation on NOS isoforms and COX-2 expression in early renal fibrogenesis in unilateral obstruction

Autores
Manucha, Walter Ariel Fernando; Oliveros, Liliana Beatriz; Carrizo, Liliana; Seltzer, Alicia Mabel; Vallesi, Patricia María
Año de publicación
2004
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
BACKGROUND: Angiotensin II plays a central role in the initiation of renal fibrogenesis at a very early stage leading to a rapid progression in unilateral ureteral obstruction (UUO). We examined the effect of an angiotensin II receptor inhibitor (AT(1)) losartan, independent from its effects on blood pressure, on nitric oxide synthase (NOS) isoforms and cyclooxygenase-2 (COX-2) expression and the significance of this interaction on interstitial fibrosis in UUO. METHODS: Rats underwent UUO for 24 hours or control sham operation after been treated with losartan in the drinking water at 10 mg/kg/day for 15 days. AT(1) receptor binding and distribution was determined by in situ autoradiographic study. Renal fibrosis was evaluated through the relative volume of the tubulointerstitium (Vv) measured by an image analyzer, and transforming growth factor-beta (TGF-beta) at mRNA levels. NOS activity, expression of NOS isoforms by reverse transcription-polymerase chain reaction (RT-PCR) assay and COX-2 protein expression, were determined. RESULTS: After administration of a nonhypotensive dose of losartan prevention of renal fibrogenesis was demonstrated in obstructed kidneys by means of Vv values and TGF-beta mRNA expression near controls. Decreased AT(1) receptor binding density was observed in cortex and inner stripe of the outer medulla of nontreated obstructed kidney compared to control, whereas no differences were observed in ipsilateral UUO related to obstructed kidney-treated group. The increased inducible NOS (iNOS) activity and expression of obstructed kidney medulla, increased neuronal NOS (nNOS), and endothelial NOS (eNOS) isoforms expression and COX-2 protein expression in obstructed kidney cortex showed down-regulation of iNOS, nNOS, and COX-2 with persistent levels of eNOS after losartan administration. CONCLUSION: These results allowed us to infer an interstitial fibrogenesis prevention independent action of losartan, involving NOS isoforms and COX-2, in unilateral obstructive nephropathy.
Fil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Fisiología; Argentina
Fil: Oliveros, Liliana Beatriz. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Fisiología; Argentina
Fil: Carrizo, Liliana. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Fisiología; Argentina
Fil: Seltzer, Alicia Mabel. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina
Fil: Vallesi, Patricia María. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Materia
COX-2
LOSARTAN
NOS ISOFORMS
TGF-Β
TUBULOINTERSTITIAL FIBROSIS
UNILATERAL URETERAL OBSTRUCTION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/169434
Acceder
id CONICETDig_5ec88987f07e36bac4c9309dc7f741df
oai_identifier_str oai:ri.conicet.gov.ar:11336/169434
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Losartan modulation on NOS isoforms and COX-2 expression in early renal fibrogenesis in unilateral obstructionManucha, Walter Ariel FernandoOliveros, Liliana BeatrizCarrizo, LilianaSeltzer, Alicia MabelVallesi, Patricia MaríaCOX-2LOSARTANNOS ISOFORMSTGF-ΒTUBULOINTERSTITIAL FIBROSISUNILATERAL URETERAL OBSTRUCTIONhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3BACKGROUND: Angiotensin II plays a central role in the initiation of renal fibrogenesis at a very early stage leading to a rapid progression in unilateral ureteral obstruction (UUO). We examined the effect of an angiotensin II receptor inhibitor (AT(1)) losartan, independent from its effects on blood pressure, on nitric oxide synthase (NOS) isoforms and cyclooxygenase-2 (COX-2) expression and the significance of this interaction on interstitial fibrosis in UUO. METHODS: Rats underwent UUO for 24 hours or control sham operation after been treated with losartan in the drinking water at 10 mg/kg/day for 15 days. AT(1) receptor binding and distribution was determined by in situ autoradiographic study. Renal fibrosis was evaluated through the relative volume of the tubulointerstitium (Vv) measured by an image analyzer, and transforming growth factor-beta (TGF-beta) at mRNA levels. NOS activity, expression of NOS isoforms by reverse transcription-polymerase chain reaction (RT-PCR) assay and COX-2 protein expression, were determined. RESULTS: After administration of a nonhypotensive dose of losartan prevention of renal fibrogenesis was demonstrated in obstructed kidneys by means of Vv values and TGF-beta mRNA expression near controls. Decreased AT(1) receptor binding density was observed in cortex and inner stripe of the outer medulla of nontreated obstructed kidney compared to control, whereas no differences were observed in ipsilateral UUO related to obstructed kidney-treated group. The increased inducible NOS (iNOS) activity and expression of obstructed kidney medulla, increased neuronal NOS (nNOS), and endothelial NOS (eNOS) isoforms expression and COX-2 protein expression in obstructed kidney cortex showed down-regulation of iNOS, nNOS, and COX-2 with persistent levels of eNOS after losartan administration. CONCLUSION: These results allowed us to infer an interstitial fibrogenesis prevention independent action of losartan, involving NOS isoforms and COX-2, in unilateral obstructive nephropathy.Fil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Fisiología; ArgentinaFil: Oliveros, Liliana Beatriz. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Fisiología; ArgentinaFil: Carrizo, Liliana. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Fisiología; ArgentinaFil: Seltzer, Alicia Mabel. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; ArgentinaFil: Vallesi, Patricia María. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaElsevier2004-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/169434Manucha, Walter Ariel Fernando; Oliveros, Liliana Beatriz; Carrizo, Liliana; Seltzer, Alicia Mabel; Vallesi, Patricia María; Losartan modulation on NOS isoforms and COX-2 expression in early renal fibrogenesis in unilateral obstruction; Elsevier; Kidney International; 65; 6; 12-2004; 2091-21070085-2538CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/j.1523-1755.2004.00643.xinfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0085253815499545info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:10:26Zoai:ri.conicet.gov.ar:11336/169434instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:10:26.689CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Losartan modulation on NOS isoforms and COX-2 expression in early renal fibrogenesis in unilateral obstruction
title Losartan modulation on NOS isoforms and COX-2 expression in early renal fibrogenesis in unilateral obstruction
spellingShingle Losartan modulation on NOS isoforms and COX-2 expression in early renal fibrogenesis in unilateral obstruction
Manucha, Walter Ariel Fernando
COX-2
LOSARTAN
NOS ISOFORMS
TGF-Β
TUBULOINTERSTITIAL FIBROSIS
UNILATERAL URETERAL OBSTRUCTION
title_short Losartan modulation on NOS isoforms and COX-2 expression in early renal fibrogenesis in unilateral obstruction
title_full Losartan modulation on NOS isoforms and COX-2 expression in early renal fibrogenesis in unilateral obstruction
title_fullStr Losartan modulation on NOS isoforms and COX-2 expression in early renal fibrogenesis in unilateral obstruction
title_full_unstemmed Losartan modulation on NOS isoforms and COX-2 expression in early renal fibrogenesis in unilateral obstruction
title_sort Losartan modulation on NOS isoforms and COX-2 expression in early renal fibrogenesis in unilateral obstruction
dc.creator.none.fl_str_mv Manucha, Walter Ariel Fernando
Oliveros, Liliana Beatriz
Carrizo, Liliana
Seltzer, Alicia Mabel
Vallesi, Patricia María
author Manucha, Walter Ariel Fernando
author_facet Manucha, Walter Ariel Fernando
Oliveros, Liliana Beatriz
Carrizo, Liliana
Seltzer, Alicia Mabel
Vallesi, Patricia María
author_role author
author2 Oliveros, Liliana Beatriz
Carrizo, Liliana
Seltzer, Alicia Mabel
Vallesi, Patricia María
author2_role author
author
author
author
dc.subject.none.fl_str_mv COX-2
LOSARTAN
NOS ISOFORMS
TGF-Β
TUBULOINTERSTITIAL FIBROSIS
UNILATERAL URETERAL OBSTRUCTION
topic COX-2
LOSARTAN
NOS ISOFORMS
TGF-Β
TUBULOINTERSTITIAL FIBROSIS
UNILATERAL URETERAL OBSTRUCTION
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv BACKGROUND: Angiotensin II plays a central role in the initiation of renal fibrogenesis at a very early stage leading to a rapid progression in unilateral ureteral obstruction (UUO). We examined the effect of an angiotensin II receptor inhibitor (AT(1)) losartan, independent from its effects on blood pressure, on nitric oxide synthase (NOS) isoforms and cyclooxygenase-2 (COX-2) expression and the significance of this interaction on interstitial fibrosis in UUO. METHODS: Rats underwent UUO for 24 hours or control sham operation after been treated with losartan in the drinking water at 10 mg/kg/day for 15 days. AT(1) receptor binding and distribution was determined by in situ autoradiographic study. Renal fibrosis was evaluated through the relative volume of the tubulointerstitium (Vv) measured by an image analyzer, and transforming growth factor-beta (TGF-beta) at mRNA levels. NOS activity, expression of NOS isoforms by reverse transcription-polymerase chain reaction (RT-PCR) assay and COX-2 protein expression, were determined. RESULTS: After administration of a nonhypotensive dose of losartan prevention of renal fibrogenesis was demonstrated in obstructed kidneys by means of Vv values and TGF-beta mRNA expression near controls. Decreased AT(1) receptor binding density was observed in cortex and inner stripe of the outer medulla of nontreated obstructed kidney compared to control, whereas no differences were observed in ipsilateral UUO related to obstructed kidney-treated group. The increased inducible NOS (iNOS) activity and expression of obstructed kidney medulla, increased neuronal NOS (nNOS), and endothelial NOS (eNOS) isoforms expression and COX-2 protein expression in obstructed kidney cortex showed down-regulation of iNOS, nNOS, and COX-2 with persistent levels of eNOS after losartan administration. CONCLUSION: These results allowed us to infer an interstitial fibrogenesis prevention independent action of losartan, involving NOS isoforms and COX-2, in unilateral obstructive nephropathy.
Fil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Fisiología; Argentina
Fil: Oliveros, Liliana Beatriz. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Fisiología; Argentina
Fil: Carrizo, Liliana. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Fisiología; Argentina
Fil: Seltzer, Alicia Mabel. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina
Fil: Vallesi, Patricia María. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Fisiología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
description BACKGROUND: Angiotensin II plays a central role in the initiation of renal fibrogenesis at a very early stage leading to a rapid progression in unilateral ureteral obstruction (UUO). We examined the effect of an angiotensin II receptor inhibitor (AT(1)) losartan, independent from its effects on blood pressure, on nitric oxide synthase (NOS) isoforms and cyclooxygenase-2 (COX-2) expression and the significance of this interaction on interstitial fibrosis in UUO. METHODS: Rats underwent UUO for 24 hours or control sham operation after been treated with losartan in the drinking water at 10 mg/kg/day for 15 days. AT(1) receptor binding and distribution was determined by in situ autoradiographic study. Renal fibrosis was evaluated through the relative volume of the tubulointerstitium (Vv) measured by an image analyzer, and transforming growth factor-beta (TGF-beta) at mRNA levels. NOS activity, expression of NOS isoforms by reverse transcription-polymerase chain reaction (RT-PCR) assay and COX-2 protein expression, were determined. RESULTS: After administration of a nonhypotensive dose of losartan prevention of renal fibrogenesis was demonstrated in obstructed kidneys by means of Vv values and TGF-beta mRNA expression near controls. Decreased AT(1) receptor binding density was observed in cortex and inner stripe of the outer medulla of nontreated obstructed kidney compared to control, whereas no differences were observed in ipsilateral UUO related to obstructed kidney-treated group. The increased inducible NOS (iNOS) activity and expression of obstructed kidney medulla, increased neuronal NOS (nNOS), and endothelial NOS (eNOS) isoforms expression and COX-2 protein expression in obstructed kidney cortex showed down-regulation of iNOS, nNOS, and COX-2 with persistent levels of eNOS after losartan administration. CONCLUSION: These results allowed us to infer an interstitial fibrogenesis prevention independent action of losartan, involving NOS isoforms and COX-2, in unilateral obstructive nephropathy.
publishDate 2004
dc.date.none.fl_str_mv 2004-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/169434
Manucha, Walter Ariel Fernando; Oliveros, Liliana Beatriz; Carrizo, Liliana; Seltzer, Alicia Mabel; Vallesi, Patricia María; Losartan modulation on NOS isoforms and COX-2 expression in early renal fibrogenesis in unilateral obstruction; Elsevier; Kidney International; 65; 6; 12-2004; 2091-2107
0085-2538
CONICET Digital
CONICET
url http://hdl.handle.net/11336/169434
identifier_str_mv Manucha, Walter Ariel Fernando; Oliveros, Liliana Beatriz; Carrizo, Liliana; Seltzer, Alicia Mabel; Vallesi, Patricia María; Losartan modulation on NOS isoforms and COX-2 expression in early renal fibrogenesis in unilateral obstruction; Elsevier; Kidney International; 65; 6; 12-2004; 2091-2107
0085-2538
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1523-1755.2004.00643.x
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0085253815499545
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.993085

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